Objective:To investigate the clinical efficacy and safety of Chuzhi Shengfa Tablets combined with ketoconazole shampoo and Chuzhi Shengfa Tablets combined with 5%minoxidil foam in the treatment of male androgenetic al...Objective:To investigate the clinical efficacy and safety of Chuzhi Shengfa Tablets combined with ketoconazole shampoo and Chuzhi Shengfa Tablets combined with 5%minoxidil foam in the treatment of male androgenetic alopecia.Methods:From July 2022 to July 2023,120 male patients with androgenetic alopecia were selected from our Department of Dermatology and randomly divided into Control Group 1,Control Group 2,Observation Group 1,and Observation Group 2,with 30 patients in each group.Control Group 1 was treated with ketoconazole shampoo,Control Group 2 with 5%minoxidil foam,Observation Group 1 with ketoconazole shampoo combined with Chuzhi Shengfa Tablets,and Observation Group 2 with 5%minoxidil foam combined with Chuzhi Shengfa Tablets.Hair density,hair diameter,scalp oil secretion(using oil secretion scoring),and adverse reactions were compared before and after treatment across the four groups.Results:After treatment,hair density and hair diameter significantly increased in all four groups compared to before treatment,while scalp oil secretion scores significantly decreased(P<0.05).The improvements in Observation Groups 1 and 2 were significantly better than those in Control Groups 1 and 2(P<0.05).No significant differences in the incidence of adverse reactions were observed among the four groups(P>0.05).Conclusion:Chuzhi Shengfa Tablets combined with ketoconazole shampoo and Chuzhi Shengfa Tablets combined with 5%minoxidil foam are both effective and safe for treating male androgenetic alopecia.These combinations can significantly improve hair growth and are worthy of clinical promotion.展开更多
Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound ...Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound Ketoconazole and Clobetasol Propionate Cream. In this work, a reliable HPLC-TOF-MS qualitative method was developed for the analysis of related substances in this preparation with a quick and easy extraction procedure. Besides the active pharmaceutical ingredients, two compounds named ketoconazole impurity B′ optical isomer and ketoconazole impurity E were identified. Furthermore, a new HPLC method for qualitative and quantitative assessment on related substances and degradation products, which were found in the stability test, was established and validated. The single standard to determine multi-components method was applied in the quantitative analysis, which was an effective way for reducing cost and improving accuracy. This study can provide a creative idea for routine analysis of quality control of the Compound Ketoconazole and Clobetasol Propionate Cream.展开更多
Objective To evaluate the incidence of Ketoconazole associated hepatotoxicity and related factors Methods Literature retrieval was conducted by using multi-databases for meta-analysis on Ketoconazole associated hepato...Objective To evaluate the incidence of Ketoconazole associated hepatotoxicity and related factors Methods Literature retrieval was conducted by using multi-databases for meta-analysis on Ketoconazole associated hepatotoxicity. The data were collected with a standardized form. Overall estimation of incidence of hepatotoxicity for specific study type was calculated by using a DerSimonian-Laird random-effects model owing to the substantial differences among the studies. Results Totally 204 eligible studies were included in the analysis. The incidence of Ketoconazole associated hepatotoxicity was 3.6%-4.2%. The dosage and duration specific subgroup analyses did not show any significant difference among groups, while the age specific subgroup analysis showed the incidence in children and people aged 〉60 years was 1.4% （95% CI 0.5%-4.2%） and 3.2% （95% Cl： 1.1%-8.7%） respectively. Additionally, the incidence of the hepatotoxicity was higher in people who had oral administration of ketoconazole beyond the provisions of the usage instructions, and the incidence was 5.7% （95% CI： 4.5%-7.2%）. Conclusion Ketoconazole associated hepatotoxicity was common. Off-label use might increase the risk of liver damage. Well-designed large sample studies are needed to identify the risk factors in future.展开更多
This paper describes a sensitive spectrophotometric method developed for determination of Ketoconazole (KC) in tablets based on amplification reactions. Ketoconazole was oxidized with periodate, resulting in formation...This paper describes a sensitive spectrophotometric method developed for determination of Ketoconazole (KC) in tablets based on amplification reactions. Ketoconazole was oxidized with periodate, resulting in formation of KC2t and iodate ions. After masking the excess periodate with molybdate, the iodate was treated with iodide to release iodine. The liberated iodine was transformed to ICl2 species and extracted as ion-pair with rhodamine 6G into toluene for spectrophotometric measurement at 535 nm. A linear calibration graph was obtained between 0.2136 mg/mL and 1.7088 mg/mL of Ketoconazole with a molar absorptivity of 5 105 mol L 1 cm 1. The procedure was successfully applied for the determination of ketoconazole in tablet formulation.展开更多
AIM： To study the long-term outcome of ketoconazole and tacrolimus combination in kidney transplant recipi-ents. METHODS： From 2006 to 2010, ketoconazole was given in 199 patients and was continued for at least 1 y...AIM： To study the long-term outcome of ketoconazole and tacrolimus combination in kidney transplant recipi-ents. METHODS： From 2006 to 2010, ketoconazole was given in 199 patients and was continued for at least 1 year or until graft failure （Group 1）, while 149 patients did not receive any ketoconazole （Group 2）. A combina-tion of tacrolimus, mycophenolate and steroid was used as maintenance therapy. High risk patients received basiliximab induction. RESULTS： Basic demographic data was similar be-tween the 2 groups. The 5-year cumulative incidence of biopsy-confrmed and clinically-treated acute rejection was signifcantly higher in Group 1 than in Group 2 （34% vs 18%, P = 0.01）. The 5-year Kaplan-Meier estimated graft survival （74.3% vs 76.4%, P = 0.58） and patient survival （87.8% vs 87.5%, P = 0.93） were not different between the 2 groups. Multivariable analyses identifed ketoconazole usage as an independent risk of acute rejection （HR = 2.33, 95%CI： 1.33-4.07; P = 0.003） while tacrolimus dose in the 2nd month was protective （HR = 0.89, 95%CI： 0.75-0.96; P = 0.041）. CONCLUSION： Co-administration of ketoconazole and tacrolimus is associated with significantly higher inci-dence of acute rejection in kidney transplant recipients.展开更多
We investigated the prognostic value of some variables of effective ketoconazole treatment for metastatic castration-resistant prostate cancer （mCRPC）. In total, 163 patients with mCRPC were eligible, receiving keto...We investigated the prognostic value of some variables of effective ketoconazole treatment for metastatic castration-resistant prostate cancer （mCRPC）. In total, 163 patients with mCRPC were eligible, receiving ketoconazole 200-400 mg three times daily with replacement doses of prednisone. Progression-free survival （PFS） was calculated from the beginning of the ketoconazole therapy to the onset of disease progression. The prognostic value of different variables for PFS was assessed by Cox regression analysis. The median PFS was 2.6 months （0.5-8.6 months） for these patients. The serum testosterone level changed during therapy, which decreased when the prostate-specific antigen （PSA） declined; the serum testosterone level increased as the levels of PSA relapsed. The median PFS values for patients associated with different factors were the following： 1.4 and 3.5 months for a nadir PSA of ≥ 0.2 and 〈0.2 ng ml- 1, respectively （hazard rate （HR）=4.767, P〈0.001）; 3.1 and 1.6 months for a baseline testosterone of ≥0.1 and 〈0.1 ng m1-1, respectively （HR=2.865, P=0.012）; 2.8 and 1.9 months for a baseline haemoglobin of ≥ 120 and 〈120 g 1-1, respectively （HR= 1.605, P〈0.001）; and 3.0 and 1.9 months for a PSA doubling time （PSADT） of ≥ 2.0 and 〈2.0 months, respectively （HR= 1.454, P=-0.017）. A risk model was constructed according to the four factors that divided patients into three subgroups of low risk （0-1 factors）, moderate risk （2 factors） and high risk （3-4 factors） with PFS values of 3.6, 3.0 and 1.4 months, respectively （HR=1.619, P〈0.001）. A nadir PSA of ≥0.2 ng m1-1, a baseline testosterone of 〈0.1 ng m1-1, a baseline haemoglobin of 〈 120 g I- 1 and a PSADT of 〈2 months were associated with a poor PFS. This risk model could provide evidence to predict the survival benefit of ketoconazole therapy.展开更多
BACKGROUND Guatemala is a developing country in Central America with limited health resources.In order to expand successful renal transplant care to children and adolescents at the lowest possible cost,our pediatric r...BACKGROUND Guatemala is a developing country in Central America with limited health resources.In order to expand successful renal transplant care to children and adolescents at the lowest possible cost,our pediatric renal transplant clinic uses a post-transplant tacrolimus-sparing strategy via inhibition of CYP3A4.AIM To study the safety,efficacy and the associated cost reduction of ketoconazole in combination with tacrolimus in this pediatric population.METHODS A retrospective chart review was carried out among the cohort of pediatric renal transplant recipients treated at the Foundation for pediatric renal patients(Fundación para el Niño Enfermo Renal-FUNDANIER),a pediatric tertiary care renal transplant center in Guatemala City,Guatemala.Patient charts were reviewed to ascertain the number of transplant recipients who were transitioned from tacrolimus based immunosuppression to combination therapy with ketoconazole and tacrolimus.Twenty-five post-transplant patients that used ketoconazole combined with tacrolimus were identified.Anthropometric,clinical and laboratory data was collected from patient charts before and after the transition.RESULTS Of the 25 patient charts reviewed 12(48%)patients were male and the average patient age was 13 years.Twenty-four(96%)transplants were from living donors.There was a non-significant difference between the mean tacrolimus doses six months and two months prior to ketoconazole:-0.10±0.04(95%CI:0.007,-0.029),P=0.23.However,the difference between the mean tacrolimus doses six months prior to ketoconazole initiation and six months after ketoconazole addition was significant:0.06±0.05(95%CI:-0.034,-0.086)P<0.001.All tacrolimus doses were reduced by 45%after the addition of ketoconazole.Therapeutic levels of tacrolimus ranged between 6.8-8.8 ng/mL during the study period and patients demonstrated an increase in estimated glomerular filtration rate.The combination of tacrolimus and ketoconazole resulted in a 21%reduction in cost.CONCLUSION Patients experienced an effective dose-reduction of tacrolimus with the administration of ketoconazole.There was no relevant variations in tacrolimus serum levels,number of rejections,or significant liver toxicity.The strategy allowed a cost reduction in pediatric immunosuppressive therapy.展开更多
Background: Ketoconazole was introduced in 1981 as the first in a series of antifungal agents that are characterized by nitrogen-containing ring. Ketoconazole acts against many different kinds of fungi such as candida...Background: Ketoconazole was introduced in 1981 as the first in a series of antifungal agents that are characterized by nitrogen-containing ring. Ketoconazole acts against many different kinds of fungi such as candida, dermatophytes and as pergillus. Also oral ketoconazole had proved its effectiveness in the treatment of cutaneous Leishmaniasis. Objective: To evaluate the safety of oral ketoconazole in the treatment of different skin diseases like cutaneous Leishmaniasis (CL), tineacapitis, tineacorporis and tineaversicolor. Patients and Methods: This is a single, blinded, therapeutic, controlled study that was carried out in the Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq, during the time, January 2015 to July 2016. In total, 951 patients with acute cutaneous leishmaniasis, tineacapitis, tineacorporis and tineaversicolor were enrolled in this study. The diagnosis was confirmed by smear and histopathology. Patients were divided into two groups: 51 patients in Group 1;24 of them were treated with oral ketoconazole tablets 200 mg twice daily for 6 weeks and 27 of them were treated orally with a combination of zinc sulfate 10 mg/kg/day and ketoconazole for 6 weeks. All patients were seen regularly every 2 weeks for 6 weeks of treatment period, then monthly for the next three months as follow up period. Liver enzymes monitoring was done for every patient in this study every two weeks. Elevated liver enzymes were considered as features of hepatotoxicity in the examined patients. While group 2 included 900 patients and was divided into 3 subgroups: A: 600 patients with tineacapitis and tineacorporis, B: 100 patients with tineaversicolor, and C: 200 patients with CL. All patients in group 2 were treated with oral KC tablets 200 mg twice daily for 6 weeks. The dose of oral KC in children is 3.3 - 6.6 mg/Kg/day. All patients in group 2 were not investigated for ketoconazole biochemical side effects but watched for any clinical symptoms and signs of any side effects. Results: After six weeks, 951 patients had completed the treatment. In the first group (51 patients), only two out 27 patients (7.4%) from the combined group showed elevated liver enzymes while the ketoconazole treated group showed no increase in liver enzymes, hence only 3.9% showed elevated liver enzymes that went to normal during follow up. In the second group (900 patients) there were no clinical symptoms and signs in favor of hepatic toxicity or other related organs. Conclusion: Ketoconazole has been used tremendously in treating of different skin diseases including fungal and Leishmania infection but without side effects, accordingly this drug seems safe to be used in treatment of different skin diseases whether adults or children.展开更多
Ketoconazole has been widely used as an antifungal drug ketoconazole shampoo. The aim of this research was to study and to that is formulated as tablets, cream and over-the-counter standardize an UV （ultraviolet spec...Ketoconazole has been widely used as an antifungal drug ketoconazole shampoo. The aim of this research was to study and to that is formulated as tablets, cream and over-the-counter standardize an UV （ultraviolet spectrophotometric） method, potentiometry and a HPLC （high performance liquid chromatographic） method for the determination ofketoconazole in commercially available tablets. These three methods were compared and discussed with respect to their sensitivity, selectivity and ready-applicability in routine analytical work. Absorption spectra and spectrophotometric determinations were carried out on the UV spectrophotometer. Investigated concentrations that ranged from 0.003 mg·dm^-3 to 0.02 mg·dm^-3. The absorbance was measured at 224 nm. In potentiometric titrations, glass and saturated （KCI） calomel electrodes were used to determine the end point of the titration. HPLC analyses of ketoconazole were carried in the presence ofeconazole as internal standard. It was concluded that the described methods are simple, fast and reliable for the identification of ketoconazole in pharmaceutical preparations. The preparation of the samples was easy, the excipients did not interfere with the active substance in the methods, so they can be used in routine quality control analysis.展开更多
Objective：To evaluate the synergistic effects of tetrandrine（TET）on the antifungal activity of topical ketoconazole（KCZ）in the treatment of dermatophytoses.Methods：The minimum inhibitory concentrations（MICs）fo...Objective：To evaluate the synergistic effects of tetrandrine（TET）on the antifungal activity of topical ketoconazole（KCZ）in the treatment of dermatophytoses.Methods：The minimum inhibitory concentrations（MICs）for KCZ and combined KCZ and TET were compared in vitro.A randomized,double-blind trial was conducted among 97 patients with dermatophytoses who were assigned to 3 groups and received： treatment with combination of 2%KZC and 2%TET cream（KCZ＋TET group）,or only 2%KZC cream（KCZ group）,or 2%TET cream（TET group）.Patients with tinea corporis and/or tinea cruris were treated for 2 weeks, separately.The patients with tinea pedis and/or tinea manuum were treated for 4 weeks.Results：Compared with KZC alone,combined use of KZC and TET showed lower MICs against clinical isolates of dermatophytes （P0.05 for all）.In the patients with tinea corporis and/or tinea cruris,the rates of overall cure（clinical cure plus mycologic clearance）were 81.25%vs.33.33%for combined treatment and KZC monotherapy,respectively, after 4 weeks.All clinical indices were significantly different between the combination therapy and only KCZ therapy groups（P0.05）.Among the patients with tinea pedis and/or tinea manuum after 4 weeks treatment,the overall cure rates in the KCZ ＋ TET group and KCZ group were 75.00%vs.40.00%,respectively.In the KCZ ＋ TET group,all the clinical indices were significantly better than those in the KCZ group and TET group（P0.05）. The rates of overall efficacy in the TET group were all zero.No local skin redness or itching was observed during TET treatment.No clinically significant changes were found in post-treatment routine blood,urine,or stool tests, ECG,or tests for liver and kidney function;no serious adverse events occurred.Conclusion：TET synergistically enhanced the clinical efficacy of topical KZC cream in the treatment of dermatophytoses.展开更多
Background： Ketoconazole （KET）, an antifungal drug, has adverse effects on the male reproductive system. Pre-treatments with antioxidant plant against testicular damage induced by KET are required. The flowers of C...Background： Ketoconazole （KET）, an antifungal drug, has adverse effects on the male reproductive system. Pre-treatments with antioxidant plant against testicular damage induced by KET are required. The flowers of Clitoria tematea （CT） are proven to have hepatoprotective potential. However, the protective effect on KET-induced testicular damage has not been reported. Objective： To investigate the protective effect of CT flower extracts with antioxidant activity on male reproductive parameters including sperm concentration, serum testosterone level, histopathology of the testis, and testicular tyrosine phosphorylation levels in rats induced with KET. Methods： The antioxidant activity of CT flower extracts was determined using 2,2-diphenyl-1-picrylhydrazyl （DPPH） and ferric reducing antioxidant power （FRAP） assays. Male rats were treated with CT flower extracts （10, 50, or 100 mg/kg BW） or distilled water via a gastric tube for 28 d （preventive period： Days 1-21） and induced by KET （100 mg/kg BW） via intraperitoneal injection for 7 d （induction period： Days 22-28）. After the experiment, all animals were examined for the weights of the testis, epididymis plus vas deferens and seminal vesicle, serum testosterone levels, sperm concentration, histological structures and diameter of testis, and testicular tyrosine phosphorylation levels by immunoblotting. Results： The CT flower extracts had capabilities for DPPH scavenging and high reducing power. At 100 mg/kg BW, the extract had no toxic effects on the male reproductive system. Significantly, in CT＋KET groups, CT flower extracts （50 and 100 mg/kg BW） alleviated the reduction of reproductive organ weight parameters, testosterone levels, and sperm concentration. In addition, CT flower extracts gave protection from testicular damage in KET-induced rats. Moreover, in the CT100＋KET group, CT flower extracts significantly enhanced the expression of a testicular 50-kDa tyrosine phosphorylated protein compared with that of other groups. Conclusions： C. ternatea flower extracts possessing antioxidant activity are not harmful to the male reproductive system and can protect against testicular damage in KET-induced rats.展开更多
AIM: To describe the long term follow-up of kidney allograft recipients receiving ketoconazole with calcineurin inhibitors(CNI) alone or combined with everolimus. METHODS: This is an open-label, prospective observatio...AIM: To describe the long term follow-up of kidney allograft recipients receiving ketoconazole with calcineurin inhibitors(CNI) alone or combined with everolimus. METHODS: This is an open-label, prospective observational clinical trial in low immunologic risk patients who, after signing an Institutional Review Board approved consent form, were included in one of two groups. The first one(n = 59) received everolimus(target blood level, 3-8 ng/m L) and the other(n = 114) azathioprine 2 mg/kg per day or mycophenolate mofetyl(MMF) 2 g/d. Both groups also received tapering steroids, the cytochrome P-450 3A4(CYP3A4) modulator, ketoconazole 50-100 mg/d, and cyclosporine with C0 targets in the everolimus group of 200-250 ng/mL in 1 mo, 100-125 ng/m L in 2 mo, and 50-65 ng/m L thereafter, and in the azathioprine or MMF group of 250-300 ng/mL in 1 mo, 200-250 ng/mL in 2 mo, 180-200 ng/m L until 3-6 mo, and 100-125 ng/mL thereafter. Clinical visits were performed monthly the first year and quarterly thereafter by treating physicians and all data was extracted by the investigators.RESULTS: The clinical characteristics of these two cohorts were similar. During the follow up(66 + 31 mo), both groups showed comparable clinical courses, but the biopsy proven acute rejection rate during the full follow-up period seemed to be lower in the everolimus group(20% vs 36%; P = 0.04). The everolimus group did not show a higher surgical complication rate thanthe other group. By the end of the follow-up period, the everolimus group tended to show a higher glomerular filtration rate. Nevertheless, we found no evidence of a consistent negative slope of the temporal allograft function estimated by the modification of the diet in renal disease formula in any of both groups. At 6 years of follow-up, the uncensored and death-censored graft survivals were 91% and 93%, and 91% and 83% in the everolimus plus cyclosporine, and cyclosporine alone groups, respectively. The addition of ketoconazole saved 80% of cyclosporine and 56% of everolimus doses. CONCLUSION: Combining CYP3A4 modulators with CNI or mammalian target of rapamycin inhibitor, in low immunological risk kidney transplant recipients is feasible, effective, safe and affordable even in the long term.展开更多
Background: Cutaneous Leishmaniasis (CL) is an endemic disease in many countries and caused by different species of Leishmania parasite. It results in a deformed scar after a relatively long period. Many therapies hav...Background: Cutaneous Leishmaniasis (CL) is an endemic disease in many countries and caused by different species of Leishmania parasite. It results in a deformed scar after a relatively long period. Many therapies have been tried in treatment of this disease. Objective: To compare the effect of oral zinc sulfate and oral ketoconazole singly and in combination in the treatment of acute cutaneous leishmaniasis. Patients and Methods: This single, blinded, therapeutic, controlled study was conducted in the Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq, during the period, January 2015 to July 2015. Seventy-five patients with acute CL were enrolled in this study. The total numbers of lesions were 327, and the duration of lesions ranged from 4 to 12 (6.9 ± 0.7) weeks. The diagnosis was confirmed by smear and histopathology. Patients were divided into three groups: 24 patients in Group A were treated with oral zinc sulfate capsules 10 mg/kg/day for 6 weeks;24 patients in Group B were treated with ketoconazole tablets 200 mg twice daily for 6 weeks and 27 patients in Group C were treated orally with a combination of zinc sulfate and ketoconazole for 6 weeks. All patients were seen regularly every 2 weeks for 6 weeks of treatment period, then monthly for the next three months as follow up period. Healing of the lesions was assessed by using Sharquie’s modified Leishmania score to assess the objective response to the topical or systemic therapy. Results:After six weeks, 75 patients have completed the treatment, 24patients received zinc sulfate capsule, 24 patients received oral ketoconazole and 27 patients received a combination of both treatments. The cure rate was (60%) in the group receiving oral zinc sulfate capsuleand (50%) in the one receiving oral ketoconazole tablet (P = 0.146) and (96%) in the combination group (P ? 0.04). Conclusion: The combination therapy using oral zinc sulfate and oral ketoconazole gave a high cure rate. The combination therapy is a new mode of therapy as both drugs act in a synergistic way.展开更多
We report a tinea capitis caused by Microsporun Canis.A 6-year-old girl who had a history contact with dogs and cats in rural area.The girl suffered from scalp mass,pustules and itching for 2 months.There were two rou...We report a tinea capitis caused by Microsporun Canis.A 6-year-old girl who had a history contact with dogs and cats in rural area.The girl suffered from scalp mass,pustules and itching for 2 months.There were two round patches in right scalp which the several pustules scattered on it.The morphology of the colony on the culture medium,the morphological characteristics under the microscope and the results of molecular sequencing confirmed that the girl’s tinea capitis was caused by Microsporun Canis.The girl was cured with the treatment of oral administration of itraconazole and ketoconazole ointment for external use for ten days.展开更多
文摘Objective:To investigate the clinical efficacy and safety of Chuzhi Shengfa Tablets combined with ketoconazole shampoo and Chuzhi Shengfa Tablets combined with 5%minoxidil foam in the treatment of male androgenetic alopecia.Methods:From July 2022 to July 2023,120 male patients with androgenetic alopecia were selected from our Department of Dermatology and randomly divided into Control Group 1,Control Group 2,Observation Group 1,and Observation Group 2,with 30 patients in each group.Control Group 1 was treated with ketoconazole shampoo,Control Group 2 with 5%minoxidil foam,Observation Group 1 with ketoconazole shampoo combined with Chuzhi Shengfa Tablets,and Observation Group 2 with 5%minoxidil foam combined with Chuzhi Shengfa Tablets.Hair density,hair diameter,scalp oil secretion(using oil secretion scoring),and adverse reactions were compared before and after treatment across the four groups.Results:After treatment,hair density and hair diameter significantly increased in all four groups compared to before treatment,while scalp oil secretion scores significantly decreased(P<0.05).The improvements in Observation Groups 1 and 2 were significantly better than those in Control Groups 1 and 2(P<0.05).No significant differences in the incidence of adverse reactions were observed among the four groups(P>0.05).Conclusion:Chuzhi Shengfa Tablets combined with ketoconazole shampoo and Chuzhi Shengfa Tablets combined with 5%minoxidil foam are both effective and safe for treating male androgenetic alopecia.These combinations can significantly improve hair growth and are worthy of clinical promotion.
文摘Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound Ketoconazole and Clobetasol Propionate Cream. In this work, a reliable HPLC-TOF-MS qualitative method was developed for the analysis of related substances in this preparation with a quick and easy extraction procedure. Besides the active pharmaceutical ingredients, two compounds named ketoconazole impurity B′ optical isomer and ketoconazole impurity E were identified. Furthermore, a new HPLC method for qualitative and quantitative assessment on related substances and degradation products, which were found in the stability test, was established and validated. The single standard to determine multi-components method was applied in the quantitative analysis, which was an effective way for reducing cost and improving accuracy. This study can provide a creative idea for routine analysis of quality control of the Compound Ketoconazole and Clobetasol Propionate Cream.
文摘Objective To evaluate the incidence of Ketoconazole associated hepatotoxicity and related factors Methods Literature retrieval was conducted by using multi-databases for meta-analysis on Ketoconazole associated hepatotoxicity. The data were collected with a standardized form. Overall estimation of incidence of hepatotoxicity for specific study type was calculated by using a DerSimonian-Laird random-effects model owing to the substantial differences among the studies. Results Totally 204 eligible studies were included in the analysis. The incidence of Ketoconazole associated hepatotoxicity was 3.6%-4.2%. The dosage and duration specific subgroup analyses did not show any significant difference among groups, while the age specific subgroup analysis showed the incidence in children and people aged 〉60 years was 1.4% （95% CI 0.5%-4.2%） and 3.2% （95% Cl： 1.1%-8.7%） respectively. Additionally, the incidence of the hepatotoxicity was higher in people who had oral administration of ketoconazole beyond the provisions of the usage instructions, and the incidence was 5.7% （95% CI： 4.5%-7.2%）. Conclusion Ketoconazole associated hepatotoxicity was common. Off-label use might increase the risk of liver damage. Well-designed large sample studies are needed to identify the risk factors in future.
文摘This paper describes a sensitive spectrophotometric method developed for determination of Ketoconazole (KC) in tablets based on amplification reactions. Ketoconazole was oxidized with periodate, resulting in formation of KC2t and iodate ions. After masking the excess periodate with molybdate, the iodate was treated with iodide to release iodine. The liberated iodine was transformed to ICl2 species and extracted as ion-pair with rhodamine 6G into toluene for spectrophotometric measurement at 535 nm. A linear calibration graph was obtained between 0.2136 mg/mL and 1.7088 mg/mL of Ketoconazole with a molar absorptivity of 5 105 mol L 1 cm 1. The procedure was successfully applied for the determination of ketoconazole in tablet formulation.
文摘AIM： To study the long-term outcome of ketoconazole and tacrolimus combination in kidney transplant recipi-ents. METHODS： From 2006 to 2010, ketoconazole was given in 199 patients and was continued for at least 1 year or until graft failure （Group 1）, while 149 patients did not receive any ketoconazole （Group 2）. A combina-tion of tacrolimus, mycophenolate and steroid was used as maintenance therapy. High risk patients received basiliximab induction. RESULTS： Basic demographic data was similar be-tween the 2 groups. The 5-year cumulative incidence of biopsy-confrmed and clinically-treated acute rejection was signifcantly higher in Group 1 than in Group 2 （34% vs 18%, P = 0.01）. The 5-year Kaplan-Meier estimated graft survival （74.3% vs 76.4%, P = 0.58） and patient survival （87.8% vs 87.5%, P = 0.93） were not different between the 2 groups. Multivariable analyses identifed ketoconazole usage as an independent risk of acute rejection （HR = 2.33, 95%CI： 1.33-4.07; P = 0.003） while tacrolimus dose in the 2nd month was protective （HR = 0.89, 95%CI： 0.75-0.96; P = 0.041）. CONCLUSION： Co-administration of ketoconazole and tacrolimus is associated with significantly higher inci-dence of acute rejection in kidney transplant recipients.
文摘We investigated the prognostic value of some variables of effective ketoconazole treatment for metastatic castration-resistant prostate cancer （mCRPC）. In total, 163 patients with mCRPC were eligible, receiving ketoconazole 200-400 mg three times daily with replacement doses of prednisone. Progression-free survival （PFS） was calculated from the beginning of the ketoconazole therapy to the onset of disease progression. The prognostic value of different variables for PFS was assessed by Cox regression analysis. The median PFS was 2.6 months （0.5-8.6 months） for these patients. The serum testosterone level changed during therapy, which decreased when the prostate-specific antigen （PSA） declined; the serum testosterone level increased as the levels of PSA relapsed. The median PFS values for patients associated with different factors were the following： 1.4 and 3.5 months for a nadir PSA of ≥ 0.2 and 〈0.2 ng ml- 1, respectively （hazard rate （HR）=4.767, P〈0.001）; 3.1 and 1.6 months for a baseline testosterone of ≥0.1 and 〈0.1 ng m1-1, respectively （HR=2.865, P=0.012）; 2.8 and 1.9 months for a baseline haemoglobin of ≥ 120 and 〈120 g 1-1, respectively （HR= 1.605, P〈0.001）; and 3.0 and 1.9 months for a PSA doubling time （PSADT） of ≥ 2.0 and 〈2.0 months, respectively （HR= 1.454, P=-0.017）. A risk model was constructed according to the four factors that divided patients into three subgroups of low risk （0-1 factors）, moderate risk （2 factors） and high risk （3-4 factors） with PFS values of 3.6, 3.0 and 1.4 months, respectively （HR=1.619, P〈0.001）. A nadir PSA of ≥0.2 ng m1-1, a baseline testosterone of 〈0.1 ng m1-1, a baseline haemoglobin of 〈 120 g I- 1 and a PSADT of 〈2 months were associated with a poor PFS. This risk model could provide evidence to predict the survival benefit of ketoconazole therapy.
文摘BACKGROUND Guatemala is a developing country in Central America with limited health resources.In order to expand successful renal transplant care to children and adolescents at the lowest possible cost,our pediatric renal transplant clinic uses a post-transplant tacrolimus-sparing strategy via inhibition of CYP3A4.AIM To study the safety,efficacy and the associated cost reduction of ketoconazole in combination with tacrolimus in this pediatric population.METHODS A retrospective chart review was carried out among the cohort of pediatric renal transplant recipients treated at the Foundation for pediatric renal patients(Fundación para el Niño Enfermo Renal-FUNDANIER),a pediatric tertiary care renal transplant center in Guatemala City,Guatemala.Patient charts were reviewed to ascertain the number of transplant recipients who were transitioned from tacrolimus based immunosuppression to combination therapy with ketoconazole and tacrolimus.Twenty-five post-transplant patients that used ketoconazole combined with tacrolimus were identified.Anthropometric,clinical and laboratory data was collected from patient charts before and after the transition.RESULTS Of the 25 patient charts reviewed 12(48%)patients were male and the average patient age was 13 years.Twenty-four(96%)transplants were from living donors.There was a non-significant difference between the mean tacrolimus doses six months and two months prior to ketoconazole:-0.10±0.04(95%CI:0.007,-0.029),P=0.23.However,the difference between the mean tacrolimus doses six months prior to ketoconazole initiation and six months after ketoconazole addition was significant:0.06±0.05(95%CI:-0.034,-0.086)P<0.001.All tacrolimus doses were reduced by 45%after the addition of ketoconazole.Therapeutic levels of tacrolimus ranged between 6.8-8.8 ng/mL during the study period and patients demonstrated an increase in estimated glomerular filtration rate.The combination of tacrolimus and ketoconazole resulted in a 21%reduction in cost.CONCLUSION Patients experienced an effective dose-reduction of tacrolimus with the administration of ketoconazole.There was no relevant variations in tacrolimus serum levels,number of rejections,or significant liver toxicity.The strategy allowed a cost reduction in pediatric immunosuppressive therapy.
文摘Background: Ketoconazole was introduced in 1981 as the first in a series of antifungal agents that are characterized by nitrogen-containing ring. Ketoconazole acts against many different kinds of fungi such as candida, dermatophytes and as pergillus. Also oral ketoconazole had proved its effectiveness in the treatment of cutaneous Leishmaniasis. Objective: To evaluate the safety of oral ketoconazole in the treatment of different skin diseases like cutaneous Leishmaniasis (CL), tineacapitis, tineacorporis and tineaversicolor. Patients and Methods: This is a single, blinded, therapeutic, controlled study that was carried out in the Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq, during the time, January 2015 to July 2016. In total, 951 patients with acute cutaneous leishmaniasis, tineacapitis, tineacorporis and tineaversicolor were enrolled in this study. The diagnosis was confirmed by smear and histopathology. Patients were divided into two groups: 51 patients in Group 1;24 of them were treated with oral ketoconazole tablets 200 mg twice daily for 6 weeks and 27 of them were treated orally with a combination of zinc sulfate 10 mg/kg/day and ketoconazole for 6 weeks. All patients were seen regularly every 2 weeks for 6 weeks of treatment period, then monthly for the next three months as follow up period. Liver enzymes monitoring was done for every patient in this study every two weeks. Elevated liver enzymes were considered as features of hepatotoxicity in the examined patients. While group 2 included 900 patients and was divided into 3 subgroups: A: 600 patients with tineacapitis and tineacorporis, B: 100 patients with tineaversicolor, and C: 200 patients with CL. All patients in group 2 were treated with oral KC tablets 200 mg twice daily for 6 weeks. The dose of oral KC in children is 3.3 - 6.6 mg/Kg/day. All patients in group 2 were not investigated for ketoconazole biochemical side effects but watched for any clinical symptoms and signs of any side effects. Results: After six weeks, 951 patients had completed the treatment. In the first group (51 patients), only two out 27 patients (7.4%) from the combined group showed elevated liver enzymes while the ketoconazole treated group showed no increase in liver enzymes, hence only 3.9% showed elevated liver enzymes that went to normal during follow up. In the second group (900 patients) there were no clinical symptoms and signs in favor of hepatic toxicity or other related organs. Conclusion: Ketoconazole has been used tremendously in treating of different skin diseases including fungal and Leishmania infection but without side effects, accordingly this drug seems safe to be used in treatment of different skin diseases whether adults or children.
文摘Ketoconazole has been widely used as an antifungal drug ketoconazole shampoo. The aim of this research was to study and to that is formulated as tablets, cream and over-the-counter standardize an UV （ultraviolet spectrophotometric） method, potentiometry and a HPLC （high performance liquid chromatographic） method for the determination ofketoconazole in commercially available tablets. These three methods were compared and discussed with respect to their sensitivity, selectivity and ready-applicability in routine analytical work. Absorption spectra and spectrophotometric determinations were carried out on the UV spectrophotometer. Investigated concentrations that ranged from 0.003 mg·dm^-3 to 0.02 mg·dm^-3. The absorbance was measured at 224 nm. In potentiometric titrations, glass and saturated （KCI） calomel electrodes were used to determine the end point of the titration. HPLC analyses of ketoconazole were carried in the presence ofeconazole as internal standard. It was concluded that the described methods are simple, fast and reliable for the identification of ketoconazole in pharmaceutical preparations. The preparation of the samples was easy, the excipients did not interfere with the active substance in the methods, so they can be used in routine quality control analysis.
基金Supported by the National Naturral Science Foundation of China(No.30972660)Foundation of Science and Technology Planning Project of Guangdong Province,China(No. 2009B030801015 and No.2008B030301350)
文摘Objective：To evaluate the synergistic effects of tetrandrine（TET）on the antifungal activity of topical ketoconazole（KCZ）in the treatment of dermatophytoses.Methods：The minimum inhibitory concentrations（MICs）for KCZ and combined KCZ and TET were compared in vitro.A randomized,double-blind trial was conducted among 97 patients with dermatophytoses who were assigned to 3 groups and received： treatment with combination of 2%KZC and 2%TET cream（KCZ＋TET group）,or only 2%KZC cream（KCZ group）,or 2%TET cream（TET group）.Patients with tinea corporis and/or tinea cruris were treated for 2 weeks, separately.The patients with tinea pedis and/or tinea manuum were treated for 4 weeks.Results：Compared with KZC alone,combined use of KZC and TET showed lower MICs against clinical isolates of dermatophytes （P0.05 for all）.In the patients with tinea corporis and/or tinea cruris,the rates of overall cure（clinical cure plus mycologic clearance）were 81.25%vs.33.33%for combined treatment and KZC monotherapy,respectively, after 4 weeks.All clinical indices were significantly different between the combination therapy and only KCZ therapy groups（P0.05）.Among the patients with tinea pedis and/or tinea manuum after 4 weeks treatment,the overall cure rates in the KCZ ＋ TET group and KCZ group were 75.00%vs.40.00%,respectively.In the KCZ ＋ TET group,all the clinical indices were significantly better than those in the KCZ group and TET group（P0.05）. The rates of overall efficacy in the TET group were all zero.No local skin redness or itching was observed during TET treatment.No clinically significant changes were found in post-treatment routine blood,urine,or stool tests, ECG,or tests for liver and kidney function;no serious adverse events occurred.Conclusion：TET synergistically enhanced the clinical efficacy of topical KZC cream in the treatment of dermatophytoses.
基金Project supported by the Faculty of Medicine,Khon Kaen University(No.I 55222),Thailand
文摘Background： Ketoconazole （KET）, an antifungal drug, has adverse effects on the male reproductive system. Pre-treatments with antioxidant plant against testicular damage induced by KET are required. The flowers of Clitoria tematea （CT） are proven to have hepatoprotective potential. However, the protective effect on KET-induced testicular damage has not been reported. Objective： To investigate the protective effect of CT flower extracts with antioxidant activity on male reproductive parameters including sperm concentration, serum testosterone level, histopathology of the testis, and testicular tyrosine phosphorylation levels in rats induced with KET. Methods： The antioxidant activity of CT flower extracts was determined using 2,2-diphenyl-1-picrylhydrazyl （DPPH） and ferric reducing antioxidant power （FRAP） assays. Male rats were treated with CT flower extracts （10, 50, or 100 mg/kg BW） or distilled water via a gastric tube for 28 d （preventive period： Days 1-21） and induced by KET （100 mg/kg BW） via intraperitoneal injection for 7 d （induction period： Days 22-28）. After the experiment, all animals were examined for the weights of the testis, epididymis plus vas deferens and seminal vesicle, serum testosterone levels, sperm concentration, histological structures and diameter of testis, and testicular tyrosine phosphorylation levels by immunoblotting. Results： The CT flower extracts had capabilities for DPPH scavenging and high reducing power. At 100 mg/kg BW, the extract had no toxic effects on the male reproductive system. Significantly, in CT＋KET groups, CT flower extracts （50 and 100 mg/kg BW） alleviated the reduction of reproductive organ weight parameters, testosterone levels, and sperm concentration. In addition, CT flower extracts gave protection from testicular damage in KET-induced rats. Moreover, in the CT100＋KET group, CT flower extracts significantly enhanced the expression of a testicular 50-kDa tyrosine phosphorylated protein compared with that of other groups. Conclusions： C. ternatea flower extracts possessing antioxidant activity are not harmful to the male reproductive system and can protect against testicular damage in KET-induced rats.
文摘AIM: To describe the long term follow-up of kidney allograft recipients receiving ketoconazole with calcineurin inhibitors(CNI) alone or combined with everolimus. METHODS: This is an open-label, prospective observational clinical trial in low immunologic risk patients who, after signing an Institutional Review Board approved consent form, were included in one of two groups. The first one(n = 59) received everolimus(target blood level, 3-8 ng/m L) and the other(n = 114) azathioprine 2 mg/kg per day or mycophenolate mofetyl(MMF) 2 g/d. Both groups also received tapering steroids, the cytochrome P-450 3A4(CYP3A4) modulator, ketoconazole 50-100 mg/d, and cyclosporine with C0 targets in the everolimus group of 200-250 ng/mL in 1 mo, 100-125 ng/m L in 2 mo, and 50-65 ng/m L thereafter, and in the azathioprine or MMF group of 250-300 ng/mL in 1 mo, 200-250 ng/mL in 2 mo, 180-200 ng/m L until 3-6 mo, and 100-125 ng/mL thereafter. Clinical visits were performed monthly the first year and quarterly thereafter by treating physicians and all data was extracted by the investigators.RESULTS: The clinical characteristics of these two cohorts were similar. During the follow up(66 + 31 mo), both groups showed comparable clinical courses, but the biopsy proven acute rejection rate during the full follow-up period seemed to be lower in the everolimus group(20% vs 36%; P = 0.04). The everolimus group did not show a higher surgical complication rate thanthe other group. By the end of the follow-up period, the everolimus group tended to show a higher glomerular filtration rate. Nevertheless, we found no evidence of a consistent negative slope of the temporal allograft function estimated by the modification of the diet in renal disease formula in any of both groups. At 6 years of follow-up, the uncensored and death-censored graft survivals were 91% and 93%, and 91% and 83% in the everolimus plus cyclosporine, and cyclosporine alone groups, respectively. The addition of ketoconazole saved 80% of cyclosporine and 56% of everolimus doses. CONCLUSION: Combining CYP3A4 modulators with CNI or mammalian target of rapamycin inhibitor, in low immunological risk kidney transplant recipients is feasible, effective, safe and affordable even in the long term.
文摘Background: Cutaneous Leishmaniasis (CL) is an endemic disease in many countries and caused by different species of Leishmania parasite. It results in a deformed scar after a relatively long period. Many therapies have been tried in treatment of this disease. Objective: To compare the effect of oral zinc sulfate and oral ketoconazole singly and in combination in the treatment of acute cutaneous leishmaniasis. Patients and Methods: This single, blinded, therapeutic, controlled study was conducted in the Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq, during the period, January 2015 to July 2015. Seventy-five patients with acute CL were enrolled in this study. The total numbers of lesions were 327, and the duration of lesions ranged from 4 to 12 (6.9 ± 0.7) weeks. The diagnosis was confirmed by smear and histopathology. Patients were divided into three groups: 24 patients in Group A were treated with oral zinc sulfate capsules 10 mg/kg/day for 6 weeks;24 patients in Group B were treated with ketoconazole tablets 200 mg twice daily for 6 weeks and 27 patients in Group C were treated orally with a combination of zinc sulfate and ketoconazole for 6 weeks. All patients were seen regularly every 2 weeks for 6 weeks of treatment period, then monthly for the next three months as follow up period. Healing of the lesions was assessed by using Sharquie’s modified Leishmania score to assess the objective response to the topical or systemic therapy. Results:After six weeks, 75 patients have completed the treatment, 24patients received zinc sulfate capsule, 24 patients received oral ketoconazole and 27 patients received a combination of both treatments. The cure rate was (60%) in the group receiving oral zinc sulfate capsuleand (50%) in the one receiving oral ketoconazole tablet (P = 0.146) and (96%) in the combination group (P ? 0.04). Conclusion: The combination therapy using oral zinc sulfate and oral ketoconazole gave a high cure rate. The combination therapy is a new mode of therapy as both drugs act in a synergistic way.
文摘We report a tinea capitis caused by Microsporun Canis.A 6-year-old girl who had a history contact with dogs and cats in rural area.The girl suffered from scalp mass,pustules and itching for 2 months.There were two round patches in right scalp which the several pustules scattered on it.The morphology of the colony on the culture medium,the morphological characteristics under the microscope and the results of molecular sequencing confirmed that the girl’s tinea capitis was caused by Microsporun Canis.The girl was cured with the treatment of oral administration of itraconazole and ketoconazole ointment for external use for ten days.
