Objective:To evaluate the effect of short term artemether administration on some blood parameters in adult male Wistar rats.Methods:Sixty five albino rats with body weight of 190-220 g were used for the four-phased st...Objective:To evaluate the effect of short term artemether administration on some blood parameters in adult male Wistar rats.Methods:Sixty five albino rats with body weight of 190-220 g were used for the four-phased study. The animals were randomly divided into five groups. The first-four groups of 15 rats were further divided into 3 subgroups of 5 rats. The drug was administered orally at sub-optimal, therapeutic, and high doses of 25, 50 and 75 mg/kg bw,respectively to the rats for 1 day, 2 days and 3 days. Blood samples were collected by cardio-puncture from the rats for hematology at the end of each phase. The last group served as control,and they were given waterad libitum.Results:Artemether caused significant reduction(P<0.05)of the hematological profile of the animals in a dose dependent manner. Discontinuation of the drug use however showed gradual recovery of the depressed indices of the blood parameters.Conclusions:The results suggest that artemether can induce reversible changes in hematological profiles of rats by extension man. This can probably aggravate anemia when artemether is administered to malaria patients. Hence, the study supports the use of the drug with cautione specially in patients prone to anemic tendencies.展开更多
Malaria is a parasitic and vector determined blood-conceived infectious disease transmitted through infected mosquitoes. Anti-malarial drug resistance is a major health problem, which hinders the control of malaria. A...Malaria is a parasitic and vector determined blood-conceived infectious disease transmitted through infected mosquitoes. Anti-malarial drug resistance is a major health problem, which hinders the control of malaria. A Results of a survey of drug-resistant malaria demonstrated safe proclivity to nearby all anti-malarial regimes accessible except from artemisinin and its derivatives. Artemether is a BCS class IV drug effective against acute and severe falciparum malaria;hence there is a strong need to improve its solubility. Silica is one of the most widely studied excipients. Silica can be used in solubility enhancement by preparing its solid solution/dispersion with the drug. The objective of this research was to improve dissolution rate of Artemether using non-precipitated porous silica(Aeroperl 300 Pharma) and precipitated silica like EXP. 9555, EXP. 9560, and EXP. 9565. Specific surface area calculated from BET method of porous silicas viz. APL 300(A), Exp. 9555(B), Exp. 9560(C), Exp. 9565(D) was found to be 294.13 m^2/g(A), 256.02 m^2/g(B), 213.62 m^2/g(C) and 207.22 m^2/g(D) respectively.The drug release from the developed formulation was found to be significantly higher as compared to neat ARM. This improved solubility and release kinetics of ARM may be attributed to high surface area, improved wettability and decreased crystallinity. Solid-state characterization of the developed optimized formulation F3 was carried out with respect to FTIR chemical imaging, XRD,SEM, and DSC. All the porous silicas which we have explored in the present context showed a significant capability as a carrier for solubility enhancement of ARM.展开更多
This study was undertaken to assess the effect of artemether treatment on plasma lipid profile in malaria infection. While the importance of lipid to plasmodial infective processes and metabolism is being increasingly...This study was undertaken to assess the effect of artemether treatment on plasma lipid profile in malaria infection. While the importance of lipid to plasmodial infective processes and metabolism is being increasingly appreciated, little is known about the attendant effect of chemotherapy on plasma lipid profile. Thirty patients with uncomplicated malaria were chosen from two secondary health-care facilities in Yobe State, Nigeria with informed consents and ethical clearance. Based on predetermined inclusion criteria patients were given 3.2 mg/kg of artemether with 1.6 mg/kg on subsequent days for a total of five days. This was done after the collection of urine and blood samples for urinalysis, malaria parasite density count and serum lipid analysis. A follow-up was planned seven (7) days from first dose during when clinical assessment and repeat malaria parasite density count and serum lipid analysis were done. Data were analyzed with statistical package for social scientist and Microsoft Excel spread sheet while level of significance at p ≤ 0.05 was calculated using paired t-test. Serum HDL cholesterol concentration recorded a significant decline of 0.13 mmol/L from a pre-treatment mean concentration of 1.17 mmol/L (p < 0.04). Triglyceride, total cholesterol, LDL-cholesterol, VLDL-cholesterol showed increment or reductions that were not significant. The clinical cure rate was 50% and mean percentage reduction in parasitaemia was 52%. A possible explanation for this low cure rate could be resistance, unfavorable pharmacokinetic disposition or lack of full adherence. A trial with complete parasite clearance, possibly using artemisinin-based combinational therapy would provide a more compelling result.展开更多
This study was conducted to establish a high performance liquid chromatography（ HPLC） method for the determination of artemether in the artemether injection using Hypersil ODS C18 chromatographic column（ 5 μm,4. 6...This study was conducted to establish a high performance liquid chromatography（ HPLC） method for the determination of artemether in the artemether injection using Hypersil ODS C18 chromatographic column（ 5 μm,4. 6 mm × 150 mm）. Mobile phase,column temperature,flow rate and detection wavelength were optimized. Acetonitrile-water-tetrahydrofuran（ 62∶ 37∶ 1,V/V） was selected as the mobile phase,and the HPLC was performed with column temperature at30 ℃ and the flow rate at 1. 0 ml/min; and the detection wavelength was set at 216 nm. The HPLC detection system of artemether had good suitability. The linearity was good in 100-800 μg/ml concentration range,and the regression equation was y = 302. 36 x-682. 02,R2= 0. 999 8. The overall average recovery was97. 58%,and the RSD was 1. 58%. Three batches of artemether injection samples were determined by the method,showing RSD of 1. 42%. The method could be used for the detection of artemether content in artemether injection.展开更多
An immunosuppressed rat model was establisbed by injecting cortisone acetate 25 mg/rat twice a week for 4 weeks and 12.5mg/rat for another 2 weeks subcutaneously.A development of Pneumocystis carinii pneumonia(PCP) wa...An immunosuppressed rat model was establisbed by injecting cortisone acetate 25 mg/rat twice a week for 4 weeks and 12.5mg/rat for another 2 weeks subcutaneously.A development of Pneumocystis carinii pneumonia(PCP) was found at the end of the 6th week in all rats.展开更多
Objective:To compare the pattern of jaundice resolution among children with severe malaria treated with quinine and artemether.Methods:Thirty two children who fulfilled the inclusion criteria were recruited for the st...Objective:To compare the pattern of jaundice resolution among children with severe malaria treated with quinine and artemether.Methods:Thirty two children who fulfilled the inclusion criteria were recruited for the study from two hospitals with intensive care facilities.They were divided into two groups:'Q' and 'A',receiving quinine and artemether.respectively.Jaundice was assessed by clinical examination.Results:Sixteen out of 32 children recruited(representing50%) presented with jaundice on the dav of recruitment.The mean age was(7.00±2.56) years.On day 3,tour patients in 'A' and six patients in 'O' had jaundice.By day 7.no child had jaundice.Conclusion:The study has shown that hoth drugs resolve jaundice although artemether relatively resolves it faster by the third day.展开更多
Objective:To explore antischitosome effects of artemether,hemin and Fe on S/LDH.Methods: Enzyme activity of rS/LDH was assayed in the standard reaction system by adding different concentration of reagents(0.00-0.10 mM...Objective:To explore antischitosome effects of artemether,hemin and Fe on S/LDH.Methods: Enzyme activity of rS/LDH was assayed in the standard reaction system by adding different concentration of reagents(0.00-0.10 mM artemether,0.00-0.02 mM hemin,0.00-0.50 mM Fe^(3+)). Same solvents of the each reagent were used as control.Results:There was no enzyme activity inhibition observed at 0.10 mM artemther:obivious inhibition for lactate oxidation reaction and pyruvate reduction reaction were detected at 0.002 mM and 0.004 mM of hemin,respectively: comparing with that of the control(P<0.05).The relative enzymatic activity inhibitions for pyruvate reduction reaction and lactate oxidation reaction at 0.02 mM hemin were 93.48%and 100.00%,respectively,comparing with that of the control(P<0.01):both pyruvate reduction and lactate oxidation reaction were inhibited completely at 0.50 mM Fe^(3+),comparing with that of the control(P<0.01).Conclusions:The results implied that SjLDH was not the direct molecular target of artemether.Hemin and Fe are inhibitors of SjLDH.展开更多
Discovered by Youyou Tu, one of the 2015 Nobel Prize winners in Physiology or Medicine, together with many other Chinese scientists, artemisinin, artemether and artesunate, as well as other artemisinins, have brought ...Discovered by Youyou Tu, one of the 2015 Nobel Prize winners in Physiology or Medicine, together with many other Chinese scientists, artemisinin, artemether and artesunate, as well as other artemisinins, have brought the global anti-malarial treatment to a new era, saving millions of lives all around the world for the past 40 years. The discoveries of artemisinins were carried out beginning from the 1970s, a special period in China, by hundreds of scientists all together under the 'whole nation' system. This article focusing on medicinal chemistry research, briefly introduced the discovery and invention course of the scientists according to the published papers, and highlighted their academic contribution and achievements. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.展开更多
文摘Objective:To evaluate the effect of short term artemether administration on some blood parameters in adult male Wistar rats.Methods:Sixty five albino rats with body weight of 190-220 g were used for the four-phased study. The animals were randomly divided into five groups. The first-four groups of 15 rats were further divided into 3 subgroups of 5 rats. The drug was administered orally at sub-optimal, therapeutic, and high doses of 25, 50 and 75 mg/kg bw,respectively to the rats for 1 day, 2 days and 3 days. Blood samples were collected by cardio-puncture from the rats for hematology at the end of each phase. The last group served as control,and they were given waterad libitum.Results:Artemether caused significant reduction(P<0.05)of the hematological profile of the animals in a dose dependent manner. Discontinuation of the drug use however showed gradual recovery of the depressed indices of the blood parameters.Conclusions:The results suggest that artemether can induce reversible changes in hematological profiles of rats by extension man. This can probably aggravate anemia when artemether is administered to malaria patients. Hence, the study supports the use of the drug with cautione specially in patients prone to anemic tendencies.
文摘Malaria is a parasitic and vector determined blood-conceived infectious disease transmitted through infected mosquitoes. Anti-malarial drug resistance is a major health problem, which hinders the control of malaria. A Results of a survey of drug-resistant malaria demonstrated safe proclivity to nearby all anti-malarial regimes accessible except from artemisinin and its derivatives. Artemether is a BCS class IV drug effective against acute and severe falciparum malaria;hence there is a strong need to improve its solubility. Silica is one of the most widely studied excipients. Silica can be used in solubility enhancement by preparing its solid solution/dispersion with the drug. The objective of this research was to improve dissolution rate of Artemether using non-precipitated porous silica(Aeroperl 300 Pharma) and precipitated silica like EXP. 9555, EXP. 9560, and EXP. 9565. Specific surface area calculated from BET method of porous silicas viz. APL 300(A), Exp. 9555(B), Exp. 9560(C), Exp. 9565(D) was found to be 294.13 m^2/g(A), 256.02 m^2/g(B), 213.62 m^2/g(C) and 207.22 m^2/g(D) respectively.The drug release from the developed formulation was found to be significantly higher as compared to neat ARM. This improved solubility and release kinetics of ARM may be attributed to high surface area, improved wettability and decreased crystallinity. Solid-state characterization of the developed optimized formulation F3 was carried out with respect to FTIR chemical imaging, XRD,SEM, and DSC. All the porous silicas which we have explored in the present context showed a significant capability as a carrier for solubility enhancement of ARM.
文摘This study was undertaken to assess the effect of artemether treatment on plasma lipid profile in malaria infection. While the importance of lipid to plasmodial infective processes and metabolism is being increasingly appreciated, little is known about the attendant effect of chemotherapy on plasma lipid profile. Thirty patients with uncomplicated malaria were chosen from two secondary health-care facilities in Yobe State, Nigeria with informed consents and ethical clearance. Based on predetermined inclusion criteria patients were given 3.2 mg/kg of artemether with 1.6 mg/kg on subsequent days for a total of five days. This was done after the collection of urine and blood samples for urinalysis, malaria parasite density count and serum lipid analysis. A follow-up was planned seven (7) days from first dose during when clinical assessment and repeat malaria parasite density count and serum lipid analysis were done. Data were analyzed with statistical package for social scientist and Microsoft Excel spread sheet while level of significance at p ≤ 0.05 was calculated using paired t-test. Serum HDL cholesterol concentration recorded a significant decline of 0.13 mmol/L from a pre-treatment mean concentration of 1.17 mmol/L (p < 0.04). Triglyceride, total cholesterol, LDL-cholesterol, VLDL-cholesterol showed increment or reductions that were not significant. The clinical cure rate was 50% and mean percentage reduction in parasitaemia was 52%. A possible explanation for this low cure rate could be resistance, unfavorable pharmacokinetic disposition or lack of full adherence. A trial with complete parasite clearance, possibly using artemisinin-based combinational therapy would provide a more compelling result.
基金Supported by Gansu Science and Technology Support Program(1604NKCA069-02)Special Fund of Agro-scientific Research in Public Interest(301303038-4)
文摘This study was conducted to establish a high performance liquid chromatography（ HPLC） method for the determination of artemether in the artemether injection using Hypersil ODS C18 chromatographic column（ 5 μm,4. 6 mm × 150 mm）. Mobile phase,column temperature,flow rate and detection wavelength were optimized. Acetonitrile-water-tetrahydrofuran（ 62∶ 37∶ 1,V/V） was selected as the mobile phase,and the HPLC was performed with column temperature at30 ℃ and the flow rate at 1. 0 ml/min; and the detection wavelength was set at 216 nm. The HPLC detection system of artemether had good suitability. The linearity was good in 100-800 μg/ml concentration range,and the regression equation was y = 302. 36 x-682. 02,R2= 0. 999 8. The overall average recovery was97. 58%,and the RSD was 1. 58%. Three batches of artemether injection samples were determined by the method,showing RSD of 1. 42%. The method could be used for the detection of artemether content in artemether injection.
文摘An immunosuppressed rat model was establisbed by injecting cortisone acetate 25 mg/rat twice a week for 4 weeks and 12.5mg/rat for another 2 weeks subcutaneously.A development of Pneumocystis carinii pneumonia(PCP) was found at the end of the 6th week in all rats.
基金sponsored by Overcomers Specialist Hospital,Ilisan Remo,Ogun State,Nigeria.Grant number:OML/RG/10/2
文摘Objective:To compare the pattern of jaundice resolution among children with severe malaria treated with quinine and artemether.Methods:Thirty two children who fulfilled the inclusion criteria were recruited for the study from two hospitals with intensive care facilities.They were divided into two groups:'Q' and 'A',receiving quinine and artemether.respectively.Jaundice was assessed by clinical examination.Results:Sixteen out of 32 children recruited(representing50%) presented with jaundice on the dav of recruitment.The mean age was(7.00±2.56) years.On day 3,tour patients in 'A' and six patients in 'O' had jaundice.By day 7.no child had jaundice.Conclusion:The study has shown that hoth drugs resolve jaundice although artemether relatively resolves it faster by the third day.
基金Supported by National Nature Science Fundation of China(No. 30860070)
文摘Objective:To explore antischitosome effects of artemether,hemin and Fe on S/LDH.Methods: Enzyme activity of rS/LDH was assayed in the standard reaction system by adding different concentration of reagents(0.00-0.10 mM artemether,0.00-0.02 mM hemin,0.00-0.50 mM Fe^(3+)). Same solvents of the each reagent were used as control.Results:There was no enzyme activity inhibition observed at 0.10 mM artemther:obivious inhibition for lactate oxidation reaction and pyruvate reduction reaction were detected at 0.002 mM and 0.004 mM of hemin,respectively: comparing with that of the control(P<0.05).The relative enzymatic activity inhibitions for pyruvate reduction reaction and lactate oxidation reaction at 0.02 mM hemin were 93.48%and 100.00%,respectively,comparing with that of the control(P<0.01):both pyruvate reduction and lactate oxidation reaction were inhibited completely at 0.50 mM Fe^(3+),comparing with that of the control(P<0.01).Conclusions:The results implied that SjLDH was not the direct molecular target of artemether.Hemin and Fe are inhibitors of SjLDH.
文摘Discovered by Youyou Tu, one of the 2015 Nobel Prize winners in Physiology or Medicine, together with many other Chinese scientists, artemisinin, artemether and artesunate, as well as other artemisinins, have brought the global anti-malarial treatment to a new era, saving millions of lives all around the world for the past 40 years. The discoveries of artemisinins were carried out beginning from the 1970s, a special period in China, by hundreds of scientists all together under the 'whole nation' system. This article focusing on medicinal chemistry research, briefly introduced the discovery and invention course of the scientists according to the published papers, and highlighted their academic contribution and achievements. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
