The main purpose of the present study was to prepare duloxetine hydrochloride(DXH) entericcoated pellets using different enteric polymers. Three layers(drug-loaded layer, barrier layer,and enteric-coated layer) were a...The main purpose of the present study was to prepare duloxetine hydrochloride(DXH) entericcoated pellets using different enteric polymers. Three layers(drug-loaded layer, barrier layer,and enteric-coated layer) were applied to the inert core pellets, successively. The optimal formulation was manufactured by employing suspension layering method in fluidized bed processor(FBP) with varieties of enteric polymers like Aqoat? AS-LF, Eudragit? L30D55 and HPMCP-HP55. The prepared pellets were measured for physical characterization and the in vitro dissolution profile. Scanning electron microscopy(SEM) was conducted to observe the morphology of pellets, and different kinetic models were applied to analyze the release mechanism of Cymbalta? and home-made pellets. The coating weight gain of enteric-coated layer containing Eudragit? L30D55, Aqoat? AS-LF and HP-55 were determined to be 35%, 26% and 24%, respectively. The similarity factors(f2) of self-made capsules with above polymers and commercially available capsules(Cymbalta?) were above 50 in the dissolution medium of pH 6.8 phosphate buffer solution(PBS). SEM figures showed the smooth surfaces of selfprepared pellets using Eudragit? L30D55 and Aqoat? AS-LF, whereas rough surface was found in the HP-55 pellets at day 0, and an impurity was appearing in the condition of 40 ℃/75% relative humidity for 1 month. In conclusion, the pellets prepared by utilizing Eudragit? L30D55 and Aqoat?AS-LF were the optimal preparations based on the dissolution profile and stability.展开更多
Background: Major depressive disorder is a serious public health problem affecting the lives of millions in the worldwide and leading causes of disability and disease. This study aimed to evaluate the efficacy and saf...Background: Major depressive disorder is a serious public health problem affecting the lives of millions in the worldwide and leading causes of disability and disease. This study aimed to evaluate the efficacy and safety of Vortioxetine and Duloxetine 60 mg compared to placebo for the treatment of major depressive disorder. Method: We searched the Cochrane library, Pub Med, CRD, Scopus, and Central Register of Controlled Trials to January 2015. We also searched ClinicalTrials.gov, International depressive disorder Conference and the Anxiety Disorders and Depression Conference. We identified that five randomized clinical trials were ultimately included in a Meta analysis. Data analysis was conducted by Standardized Mean Differences (SMD) for Montgomery-Åsberg Depression Rating Scale (MADRS), and Odds Ratio (OR) for adverse events. The SMD and OR reported by 95% CI. Results: Results showed statistical significance in the MADRS for Vortioxetine (SMD = ﹣3.29;95% CI ﹣4.47 to ﹣2.10;I2 = 99.3%) and for Duloxetine 60 mg (SMD = ﹣6.35;95% CI ﹣8.84, ﹣3.87;I2 = 99.3%). Results showed that the Vortioxetine 2.5, 5, 10, 15, 20 mg and overall compared to placebo showed a significance for Nausea and no significance for diarrhea, dry mouth, dizziness, fatigue and headache. Also results of Duloxetine 60 mg showed a significant effect for dry mouth, dizziness, fatigue and nausea. Conclusion: It is necessary to do more studies so as to better assess and much more powerful than the evidence for the use of this drug in the treatment of depression.展开更多
To compare remission rate, relapse rate and tolerability of duloxetine, a dual reuptake inhibitor of 5-hydroxy serotonin (5-HT) and norepinephrine (NE), versus fluoxetine, a reuptake inhibitor of 5-HT during follow up...To compare remission rate, relapse rate and tolerability of duloxetine, a dual reuptake inhibitor of 5-hydroxy serotonin (5-HT) and norepinephrine (NE), versus fluoxetine, a reuptake inhibitor of 5-HT during follow up period of 16 weeks in major depressive disorder (MDD) a open label comparative trial was conducted. Trial was comprising of 60 patients, diagnosed with MDD, were allocated to fluoxetine group (n*-30, 20-60mg od) or duloxetine group (n*-30, 40-60mg od) for 16 weeks. The end points were remission and relapse assessed by Hamilton Rating scale for Depression-24 items (HAMD-24). In results the mean fall in HAMD-24 scores between groups was comparable till 4 weeks. Thereafter, at 8 weeks the mean fall in HAMD-24 score was significantly greater in duloxetine group (p value < 0.05). At 16 weeks the mean fall was highly significant (p value < 0.01) in duloxetine group. Thirty percent patients in duloxetine group achieved remission in comparison to none in fluoxetine group. None of the patient, in any group, reported relapse. Adverse effects were mild to moderate in severity.In conclusion duloxetine has a better pharmacological profile over fluoxetine in terms of efficacy and safety.展开更多
Objective: Chemotherapy with paclitaxel is associated with significant neurotoxicity that may offset patients' quality of life and therapeutic benefits. This prospective, non-randomized control study evaluated the...Objective: Chemotherapy with paclitaxel is associated with significant neurotoxicity that may offset patients' quality of life and therapeutic benefits. This prospective, non-randomized control study evaluated the efficacy and safety of an antidepressant drug, duloxetine, at 30 or 60 mg/d, in the treatment of paclitaxel-induced peripheral neuropathy(PIPN) in Chinese breast cancer patients.Methods:A total of 102 patients with a median age of 50(range,25–60)years,treated in the Department of Medical Oncology,National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,between November 2014 and January 2017 were finally enrolled.Stratified by baseline characteristics,the patients were classified into two groups,receiving either duloxetine or alternative antineurotoxicity drugs.During the course of the paclitaxel regimen,the eligibility criteria included sensory neuropathy,as evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events.The treatment consisted of receiving 30 mg duloxetine(for the first 4 weeks)and 60 mg duloxetine for an additional 8 weeks,or any other anti-neurotoxicity drug daily during the same crossover period.The improvement associated with PIPN from the patient’s perspective were assessed by the Functional Assessment of Cancer Therapy-Taxane(FACT-Tax)Scales,which contained questions scored from 0 to 4(0,not at all;4,very much;total score range,0–44).Results:Duloxetine was more effective in decreasing PIPN(odds ratio=5.426;95%confidence interval,1.898–15.514;P=0.002).Between duloxetine group and control group,the median(25th–75th percentiles)decreasing difference in the FACT-Tax pain score was 4(2–6)vs.1(0–4)(P=0.005).Conclusions:Duloxetine is a promising and safe option with tolerable toxicity at a dose of 60 mg/d for Chinese breast cancer patients with PIPN.Non-neuropathy adverse events were mild and similar in both groups.The major toxicities of duloxetine included nausea,constipation,somnolence,dizziness and distention of the eyes.Further examination of the benefits of duloxetine in the prevention of PIPN is required.展开更多
This paper describes a simple, rapid and sensitive liquid chromatography-tandem mass spectrometry assay for the determination of duloxetine in human plasma. A duloxetine stable labeled isotope (duloxetine d 5 ) was us...This paper describes a simple, rapid and sensitive liquid chromatography-tandem mass spectrometry assay for the determination of duloxetine in human plasma. A duloxetine stable labeled isotope (duloxetine d 5 ) was used as an internal standard. Analyte and the internal standard were extracted from 100 mL of human plasma via solid phase extraction technique using Oasis HLB cartridges. The chromatographic separation was achieved on a C 18 column by using a mixture of acetonitrile-5 mM ammonium acetate buffer (83:17, v/v) as the mobile phase at a flow rate of 0.9 mL/min. The calibration curve obtained was linear (r 2 Z0.99) over the concentration range of 0.05-101 ng/mL. Multiple-reaction monitoring mode (MRM) was used for quantification of ion transitions at m/z 298.3/154.1 and 303.3/159.1 for the drug and the internal standard, respectively. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 2.5 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies.展开更多
BACKGROUND Toxic epidermal necrolysis(TEN)is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions.Standard management includes discontinuation of culprit drug and application o...BACKGROUND Toxic epidermal necrolysis(TEN)is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions.Standard management includes discontinuation of culprit drug and application of immunomodulatory therapy.However,mortality remains high due to complications like septic shock and multiorgan failures.Innovative approaches for skin care are crucial.This report introduces borneol-gypsum,a traditional Chinese drug but a novel dressing serving as an adjuvant of TEN therapy,might significantly improve skin conditions and patient outcomes in TEN.CASE SUMMARY A 38-year-old woman diagnosed with eosinophilic granulomatosis with polyangiitis experienced gangrenous complications and motor nerve involvement.After initial treatment of high-dose corticosteroids and cyclophosphamide,symptom of foot drop improved,absolute eosinophil counts decreased,while limb pain sustained.Duloxetine was added to alleviate her symptom.Subsequently,TEN developed.Additional topical application of borneol-gypsum dressing not only protected the skin lesions from infection but also significantly eased localized pain.This approach demonstrated its merit in TEN management by promoting skin healing and potentially reducing infection risks.CONCLUSION Borneol-gypsum dressing is a promising adjuvant that could significantly improve TEN management,skin regeneration,and patient comfort.展开更多
Duloxetine(DUL), an antidepressant drug, has been detected in surface water and wastewater effluents, however, there is little information on the formation of its transformation products(TPs). In this work, hydrolysis...Duloxetine(DUL), an antidepressant drug, has been detected in surface water and wastewater effluents, however, there is little information on the formation of its transformation products(TPs). In this work, hydrolysis, photodegradation(UV irradiation) and chlorination experiments were performed on spiked distillated water, under controlled experimental conditions to simulate abiotic processes that can occur in the environment and wastewater treatment plants(WWTPs). Eleven TPs, nine from reaction with UV light and two from chlorine contact, were formed and detected by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry, and nine of them had their chemical structures elucidated upon analyses of their fragmentation patterns in MS/MS spectra. The formation and degradation of the TPs were observed. The parent compound was completely degraded after30 min in photodegradation and after 24 hr in chlorination. Almost all TPs were completely degraded in the experiments. The ecotoxicity and mutagenicity of the TPs were predicted based on several in silico models and it was found that a few of these products presented more ecotoxicity than DUL itself and six TPs showed positive mutagenicity. Finally, wastewater samples were analyzed and DUL and one TP, possibly formed by chlorination process, were detected in the effluent, which showed that WWTP not only did not remove DUL, but also formed a TP.展开更多
Cancer-related fatigue(CRF)is a common polysymptomatic syndrome with no standard therapy.The authors present the case of a prostate cancer patient in whom,during hormone therapy,disabling CRF and urinary incontinence ...Cancer-related fatigue(CRF)is a common polysymptomatic syndrome with no standard therapy.The authors present the case of a prostate cancer patient in whom,during hormone therapy,disabling CRF and urinary incontinence occurred.CRF was assessed according to the brief fatigue inventory(BFI).The patient received duloxetine,60 mg daily,due to its impact on both CRF and incontinence.After 2 months,the BFI score decreased(from 9 to 2)and urinary incontinence resolved.After duloxetine discontinuation,the patient maintained a low BFI score.The authors conclude that,as a serotonin-noradrenaline reuptake inhibitor,duloxetine could be active on prostate CRF,especially with associated urinary symptoms.Therefore,a pilot placebo-controlled trial with duloxetine to treat prostate CRF may be worthwhile.展开更多
文摘The main purpose of the present study was to prepare duloxetine hydrochloride(DXH) entericcoated pellets using different enteric polymers. Three layers(drug-loaded layer, barrier layer,and enteric-coated layer) were applied to the inert core pellets, successively. The optimal formulation was manufactured by employing suspension layering method in fluidized bed processor(FBP) with varieties of enteric polymers like Aqoat? AS-LF, Eudragit? L30D55 and HPMCP-HP55. The prepared pellets were measured for physical characterization and the in vitro dissolution profile. Scanning electron microscopy(SEM) was conducted to observe the morphology of pellets, and different kinetic models were applied to analyze the release mechanism of Cymbalta? and home-made pellets. The coating weight gain of enteric-coated layer containing Eudragit? L30D55, Aqoat? AS-LF and HP-55 were determined to be 35%, 26% and 24%, respectively. The similarity factors(f2) of self-made capsules with above polymers and commercially available capsules(Cymbalta?) were above 50 in the dissolution medium of pH 6.8 phosphate buffer solution(PBS). SEM figures showed the smooth surfaces of selfprepared pellets using Eudragit? L30D55 and Aqoat? AS-LF, whereas rough surface was found in the HP-55 pellets at day 0, and an impurity was appearing in the condition of 40 ℃/75% relative humidity for 1 month. In conclusion, the pellets prepared by utilizing Eudragit? L30D55 and Aqoat?AS-LF were the optimal preparations based on the dissolution profile and stability.
文摘Background: Major depressive disorder is a serious public health problem affecting the lives of millions in the worldwide and leading causes of disability and disease. This study aimed to evaluate the efficacy and safety of Vortioxetine and Duloxetine 60 mg compared to placebo for the treatment of major depressive disorder. Method: We searched the Cochrane library, Pub Med, CRD, Scopus, and Central Register of Controlled Trials to January 2015. We also searched ClinicalTrials.gov, International depressive disorder Conference and the Anxiety Disorders and Depression Conference. We identified that five randomized clinical trials were ultimately included in a Meta analysis. Data analysis was conducted by Standardized Mean Differences (SMD) for Montgomery-Åsberg Depression Rating Scale (MADRS), and Odds Ratio (OR) for adverse events. The SMD and OR reported by 95% CI. Results: Results showed statistical significance in the MADRS for Vortioxetine (SMD = ﹣3.29;95% CI ﹣4.47 to ﹣2.10;I2 = 99.3%) and for Duloxetine 60 mg (SMD = ﹣6.35;95% CI ﹣8.84, ﹣3.87;I2 = 99.3%). Results showed that the Vortioxetine 2.5, 5, 10, 15, 20 mg and overall compared to placebo showed a significance for Nausea and no significance for diarrhea, dry mouth, dizziness, fatigue and headache. Also results of Duloxetine 60 mg showed a significant effect for dry mouth, dizziness, fatigue and nausea. Conclusion: It is necessary to do more studies so as to better assess and much more powerful than the evidence for the use of this drug in the treatment of depression.
文摘To compare remission rate, relapse rate and tolerability of duloxetine, a dual reuptake inhibitor of 5-hydroxy serotonin (5-HT) and norepinephrine (NE), versus fluoxetine, a reuptake inhibitor of 5-HT during follow up period of 16 weeks in major depressive disorder (MDD) a open label comparative trial was conducted. Trial was comprising of 60 patients, diagnosed with MDD, were allocated to fluoxetine group (n*-30, 20-60mg od) or duloxetine group (n*-30, 40-60mg od) for 16 weeks. The end points were remission and relapse assessed by Hamilton Rating scale for Depression-24 items (HAMD-24). In results the mean fall in HAMD-24 scores between groups was comparable till 4 weeks. Thereafter, at 8 weeks the mean fall in HAMD-24 score was significantly greater in duloxetine group (p value < 0.05). At 16 weeks the mean fall was highly significant (p value < 0.01) in duloxetine group. Thirty percent patients in duloxetine group achieved remission in comparison to none in fluoxetine group. None of the patient, in any group, reported relapse. Adverse effects were mild to moderate in severity.In conclusion duloxetine has a better pharmacological profile over fluoxetine in terms of efficacy and safety.
文摘Objective: Chemotherapy with paclitaxel is associated with significant neurotoxicity that may offset patients' quality of life and therapeutic benefits. This prospective, non-randomized control study evaluated the efficacy and safety of an antidepressant drug, duloxetine, at 30 or 60 mg/d, in the treatment of paclitaxel-induced peripheral neuropathy(PIPN) in Chinese breast cancer patients.Methods:A total of 102 patients with a median age of 50(range,25–60)years,treated in the Department of Medical Oncology,National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,between November 2014 and January 2017 were finally enrolled.Stratified by baseline characteristics,the patients were classified into two groups,receiving either duloxetine or alternative antineurotoxicity drugs.During the course of the paclitaxel regimen,the eligibility criteria included sensory neuropathy,as evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events.The treatment consisted of receiving 30 mg duloxetine(for the first 4 weeks)and 60 mg duloxetine for an additional 8 weeks,or any other anti-neurotoxicity drug daily during the same crossover period.The improvement associated with PIPN from the patient’s perspective were assessed by the Functional Assessment of Cancer Therapy-Taxane(FACT-Tax)Scales,which contained questions scored from 0 to 4(0,not at all;4,very much;total score range,0–44).Results:Duloxetine was more effective in decreasing PIPN(odds ratio=5.426;95%confidence interval,1.898–15.514;P=0.002).Between duloxetine group and control group,the median(25th–75th percentiles)decreasing difference in the FACT-Tax pain score was 4(2–6)vs.1(0–4)(P=0.005).Conclusions:Duloxetine is a promising and safe option with tolerable toxicity at a dose of 60 mg/d for Chinese breast cancer patients with PIPN.Non-neuropathy adverse events were mild and similar in both groups.The major toxicities of duloxetine included nausea,constipation,somnolence,dizziness and distention of the eyes.Further examination of the benefits of duloxetine in the prevention of PIPN is required.
基金We thank the National Natural Science Foundation of China （No. 20472061）；Guangzhou Bureau of Science and Technology for financial support of this study.
文摘This paper describes a simple, rapid and sensitive liquid chromatography-tandem mass spectrometry assay for the determination of duloxetine in human plasma. A duloxetine stable labeled isotope (duloxetine d 5 ) was used as an internal standard. Analyte and the internal standard were extracted from 100 mL of human plasma via solid phase extraction technique using Oasis HLB cartridges. The chromatographic separation was achieved on a C 18 column by using a mixture of acetonitrile-5 mM ammonium acetate buffer (83:17, v/v) as the mobile phase at a flow rate of 0.9 mL/min. The calibration curve obtained was linear (r 2 Z0.99) over the concentration range of 0.05-101 ng/mL. Multiple-reaction monitoring mode (MRM) was used for quantification of ion transitions at m/z 298.3/154.1 and 303.3/159.1 for the drug and the internal standard, respectively. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 2.5 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies.
文摘BACKGROUND Toxic epidermal necrolysis(TEN)is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions.Standard management includes discontinuation of culprit drug and application of immunomodulatory therapy.However,mortality remains high due to complications like septic shock and multiorgan failures.Innovative approaches for skin care are crucial.This report introduces borneol-gypsum,a traditional Chinese drug but a novel dressing serving as an adjuvant of TEN therapy,might significantly improve skin conditions and patient outcomes in TEN.CASE SUMMARY A 38-year-old woman diagnosed with eosinophilic granulomatosis with polyangiitis experienced gangrenous complications and motor nerve involvement.After initial treatment of high-dose corticosteroids and cyclophosphamide,symptom of foot drop improved,absolute eosinophil counts decreased,while limb pain sustained.Duloxetine was added to alleviate her symptom.Subsequently,TEN developed.Additional topical application of borneol-gypsum dressing not only protected the skin lesions from infection but also significantly eased localized pain.This approach demonstrated its merit in TEN management by promoting skin healing and potentially reducing infection risks.CONCLUSION Borneol-gypsum dressing is a promising adjuvant that could significantly improve TEN management,skin regeneration,and patient comfort.
基金supported by Brazilian Federal Agency Coordenacao de Aperfeicoamento de Pessoal de Nível Superior(CAPES)for PhD grants(No.99999.000845/2014-00)Fundacao para a Ciência e a Tecnologia(FCT)Portugal(Projects UID/MULTI/00612/2013,PEst-OE/QUI/UI0612/2013 and LISBOA-01-0145-FEDER-022125)
文摘Duloxetine(DUL), an antidepressant drug, has been detected in surface water and wastewater effluents, however, there is little information on the formation of its transformation products(TPs). In this work, hydrolysis, photodegradation(UV irradiation) and chlorination experiments were performed on spiked distillated water, under controlled experimental conditions to simulate abiotic processes that can occur in the environment and wastewater treatment plants(WWTPs). Eleven TPs, nine from reaction with UV light and two from chlorine contact, were formed and detected by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry, and nine of them had their chemical structures elucidated upon analyses of their fragmentation patterns in MS/MS spectra. The formation and degradation of the TPs were observed. The parent compound was completely degraded after30 min in photodegradation and after 24 hr in chlorination. Almost all TPs were completely degraded in the experiments. The ecotoxicity and mutagenicity of the TPs were predicted based on several in silico models and it was found that a few of these products presented more ecotoxicity than DUL itself and six TPs showed positive mutagenicity. Finally, wastewater samples were analyzed and DUL and one TP, possibly formed by chlorination process, were detected in the effluent, which showed that WWTP not only did not remove DUL, but also formed a TP.
文摘Cancer-related fatigue(CRF)is a common polysymptomatic syndrome with no standard therapy.The authors present the case of a prostate cancer patient in whom,during hormone therapy,disabling CRF and urinary incontinence occurred.CRF was assessed according to the brief fatigue inventory(BFI).The patient received duloxetine,60 mg daily,due to its impact on both CRF and incontinence.After 2 months,the BFI score decreased(from 9 to 2)and urinary incontinence resolved.After duloxetine discontinuation,the patient maintained a low BFI score.The authors conclude that,as a serotonin-noradrenaline reuptake inhibitor,duloxetine could be active on prostate CRF,especially with associated urinary symptoms.Therefore,a pilot placebo-controlled trial with duloxetine to treat prostate CRF may be worthwhile.
