To study the bioequivalence of Clavulanate Potassium and Amoxicillin (1:7) dispersible tablets, a randomized cross over study was conducted in 18 healthy volunteers. A single oral dose of 1000 mg Clav ulanate Pot...To study the bioequivalence of Clavulanate Potassium and Amoxicillin (1:7) dispersible tablets, a randomized cross over study was conducted in 18 healthy volunteers. A single oral dose of 1000 mg Clav ulanate Potassium and Amoxicillin (1:7) dispersible tablets (Tested formulation, T) or Augmentin syrup (Reference formulation, R). Concentrations in plasma were determined with high performance liquid chromatography. The main paramaters of T were: for Clavulanate Potassium and Amoxicillin, C max : 2.46±1.11 μg/m l and 18.81±7.26 μg/ml, T max : 1.12±0.23h and 1.30±0.34h, AUC (0 - 6 h) : 5.18±2.24 μg·h/ml and 45.09±14.53 μg·h/ml, t 1/2 : 1.43±0.44 h and 1.09±0.22 h., respectively. The relative bioavailability of T to R were 9 6.5±19.2 % and 98.4±26.1 % , respectively. Statistical analysis showed that th e two formulations were bioequivalent.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
文摘To study the bioequivalence of Clavulanate Potassium and Amoxicillin (1:7) dispersible tablets, a randomized cross over study was conducted in 18 healthy volunteers. A single oral dose of 1000 mg Clav ulanate Potassium and Amoxicillin (1:7) dispersible tablets (Tested formulation, T) or Augmentin syrup (Reference formulation, R). Concentrations in plasma were determined with high performance liquid chromatography. The main paramaters of T were: for Clavulanate Potassium and Amoxicillin, C max : 2.46±1.11 μg/m l and 18.81±7.26 μg/ml, T max : 1.12±0.23h and 1.30±0.34h, AUC (0 - 6 h) : 5.18±2.24 μg·h/ml and 45.09±14.53 μg·h/ml, t 1/2 : 1.43±0.44 h and 1.09±0.22 h., respectively. The relative bioavailability of T to R were 9 6.5±19.2 % and 98.4±26.1 % , respectively. Statistical analysis showed that th e two formulations were bioequivalent.
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.
