OBJECTIVE To enhance the quality and efficiency of chlorogeninc acid by investigating the differences among the chlorogeninc acid polymorphs in bioavailability and solubility.METHODS Determinative method was used to a...OBJECTIVE To enhance the quality and efficiency of chlorogeninc acid by investigating the differences among the chlorogeninc acid polymorphs in bioavailability and solubility.METHODS Determinative method was used to analyze the solubility of chlorogeninc acid polymorphs;solid chlorogeninc acid in different forms were orally administered to the rats,and a HPLC method was established to determinate plasma lever of metabolite-acyclovir and the bioavailability was analyzed.RESULTS The indirect pharmacokinetic parameters of Chlorogeninc acid,as the metabolites of the form Ⅰ,Ⅱ,Ⅲ,were as follows:cmaxwas 0.37,0.34 and 0.44mg·L-1,respectively;AUC0→twas 0.71,0.76 and 0.79mg·L-1·h,respectively.CONCLUSION The solubility of form Ⅲ was larger than the other forms′.The solubility of Chlorogeninc acid polymorphs:form Ⅰ,form Ⅱ,form Ⅲ were merely the same,there was no statistically significant difference in pharmacokinetic parameters among these three forms.展开更多
OBJECTIVE To explain the high inter-individual variability and the frequency of exceeding the therapeutic reference range and the laboratory alert level of amisulpride,a popula⁃tion pharmacokinetic model in Chinese pa...OBJECTIVE To explain the high inter-individual variability and the frequency of exceeding the therapeutic reference range and the laboratory alert level of amisulpride,a popula⁃tion pharmacokinetic model in Chinese patients with schizophrenia was built based on therapeu⁃tic drug monitoring data to guide individualized therapy.METHODS Plasma concentration data(330 measurements from 121 patients)were ana⁃lyzed using a nonlinear mixed-effects model⁃ing approach with first-order conditional estima⁃tion with interaction(FOCE I).The concentra⁃tions of amisulpride were detected by HPLC-MS/MS.Age,weight,sex,combination medication history and renal function status were evaluated as main covariates.The model was internally val⁃idated using goodness-of-fit,bootstrap and nor⁃malized prediction distribution error.Recom⁃mended dosage regimens for patients with key covariates were estimated on the basis of Monte Carlo simulations and the established model.RESULTS A one-compartment model with first-order absorption and elimination was found to adequately characterize amisulpride concentra⁃tion in Chinese patients with schizophrenia.The population estimates of the apparent volume of distribution(V/F)and apparent clearance(CL/F)were 12.7 L and 1.12 L·h-1,respectively.Age sig⁃nificantly affected the clearance of amisulpride and the final model was as follow:CL/F=1.04×(AGE/32)-0.624(L·h-1).To avoid exceeding the lab⁃oratory alert level(640μg·L-1),the model-based simulation results showed that the recommended dose of amisulpride was no more than 600 mg per day for patients aged 60 years,800 mg per day for those aged 40 years and 1200 mg per day for those aged 20 years,respectively.CON⁃CLUSION Dosage optimization of amisulpride can be carried out according to age to reduce the risk of adverse reactions.The model can be used as a suitable tool for designing individual⁃ized therapy for Chinese patients with schizo⁃phrenia.展开更多
基金The project supported by the Ministry of Science and Technology of China(2007FY130100)the 12th Five-Year Plan project(2012ZX09301002-001-013)
文摘OBJECTIVE To enhance the quality and efficiency of chlorogeninc acid by investigating the differences among the chlorogeninc acid polymorphs in bioavailability and solubility.METHODS Determinative method was used to analyze the solubility of chlorogeninc acid polymorphs;solid chlorogeninc acid in different forms were orally administered to the rats,and a HPLC method was established to determinate plasma lever of metabolite-acyclovir and the bioavailability was analyzed.RESULTS The indirect pharmacokinetic parameters of Chlorogeninc acid,as the metabolites of the form Ⅰ,Ⅱ,Ⅲ,were as follows:cmaxwas 0.37,0.34 and 0.44mg·L-1,respectively;AUC0→twas 0.71,0.76 and 0.79mg·L-1·h,respectively.CONCLUSION The solubility of form Ⅲ was larger than the other forms′.The solubility of Chlorogeninc acid polymorphs:form Ⅰ,form Ⅱ,form Ⅲ were merely the same,there was no statistically significant difference in pharmacokinetic parameters among these three forms.
文摘OBJECTIVE To explain the high inter-individual variability and the frequency of exceeding the therapeutic reference range and the laboratory alert level of amisulpride,a popula⁃tion pharmacokinetic model in Chinese patients with schizophrenia was built based on therapeu⁃tic drug monitoring data to guide individualized therapy.METHODS Plasma concentration data(330 measurements from 121 patients)were ana⁃lyzed using a nonlinear mixed-effects model⁃ing approach with first-order conditional estima⁃tion with interaction(FOCE I).The concentra⁃tions of amisulpride were detected by HPLC-MS/MS.Age,weight,sex,combination medication history and renal function status were evaluated as main covariates.The model was internally val⁃idated using goodness-of-fit,bootstrap and nor⁃malized prediction distribution error.Recom⁃mended dosage regimens for patients with key covariates were estimated on the basis of Monte Carlo simulations and the established model.RESULTS A one-compartment model with first-order absorption and elimination was found to adequately characterize amisulpride concentra⁃tion in Chinese patients with schizophrenia.The population estimates of the apparent volume of distribution(V/F)and apparent clearance(CL/F)were 12.7 L and 1.12 L·h-1,respectively.Age sig⁃nificantly affected the clearance of amisulpride and the final model was as follow:CL/F=1.04×(AGE/32)-0.624(L·h-1).To avoid exceeding the lab⁃oratory alert level(640μg·L-1),the model-based simulation results showed that the recommended dose of amisulpride was no more than 600 mg per day for patients aged 60 years,800 mg per day for those aged 40 years and 1200 mg per day for those aged 20 years,respectively.CON⁃CLUSION Dosage optimization of amisulpride can be carried out according to age to reduce the risk of adverse reactions.The model can be used as a suitable tool for designing individual⁃ized therapy for Chinese patients with schizo⁃phrenia.
