Pharmacokinetic and pharmacodynamic population modeling of orally administered rabeprazole in healthy Chinese volunteers by the NONMEM method
| Autor: | Rui-Yuan Sun, Zhi-Yang Chen, Gang Hu, Haitang Xie, Qing-Shan Zheng |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Population Rabeprazole Pharmacology High-performance liquid chromatography Models Biological 2-Pyridinylmethylsulfinylbenzimidazoles Mixed Function Oxygenases Pharmacokinetics Oral administration medicine Humans Pharmacology (medical) education Chromatography High Pressure Liquid EC50 education.field_of_study Chemistry Reverse Transcriptase Polymerase Chain Reaction Hydrogen-Ion Concentration Anti-Ulcer Agents NONMEM Cytochrome P-450 CYP2C19 Nonlinear Dynamics Pharmacodynamics Benzimidazoles Aryl Hydrocarbon Hydroxylases Algorithms Omeprazole medicine.drug |
| Zdroj: | European journal of drug metabolism and pharmacokinetics. 31(1) |
| ISSN: | 0378-7966 |
| Popis: | The pharmacokinetic-pharmacodynamic (PK-PD) relationship of the proton pump inhibitor rabeprazole in healthy Chinese volunteers was characterized via a population approach. Healthy Chinese male volunteers were enrolled in the clinical trial. Subjects were divided into three groups by their CYP2C19 genotype. Serum concentrations of rabeprazole were determined using high performance liquid chromatography (HPLC). The intragastric pH values were monitored simultaneously. Data analysis was performed using nonlinear mixed-effects modeling as implemented in the NONMEM software package. The final PK-PD model incorporated a one-compartment PK model with one-order absorption from the gastroenteric trace, first-order elimination pathway with one fixed-effect genotype modeling, and a full sigmoidal Emax PD model (X +/- SE: E0 = 2.30 +/- 0.189; Emax = 7.32 +/- 0.662; EC50 = 51.3 +/- 2.142 ng/ml; Hill coefficient = 5.00 +/- 0.556). The time profiles for concentration and pH value, as well as the concentration-pH value relationship of rabeprazole in healthy Chinese volunteers were well described by the developed population PK-PD model. |
| Databáze: | OpenAIRE |
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