S-warfarin limited sampling strategy with a population pharmacokinetic approach to estimate exposure and cytochrome P450 (CYP) 2C9 activity in healthy adults
Autor: | Sandrine Turpault, Joseph D. Ma, Edmund V. Capparelli, Lana Tran, Joseph S. Bertino, Angela D. M. Kashuba, Anne N. Nafziger, Mina Nikanjam |
---|---|
Rok vydání: | 2021 |
Předmět: |
Pharmacology
Volume of distribution medicine.medical_specialty education.field_of_study Correlation coefficient business.industry Population Sampling (statistics) Lopinavir General Medicine 030226 pharmacology & pharmacy Gastroenterology 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine Medicine Pharmacology (medical) Ritonavir 030212 general & internal medicine business education CYP2C9 medicine.drug |
Zdroj: | European Journal of Clinical Pharmacology. 77:1349-1356 |
ISSN: | 1432-1041 0031-6970 |
Popis: | S-warfarin is used to phenotype cytochrome P450 (CYP) 2C9 activity. This study evaluated S-warfarin limited sampling strategy with a population pharmacokinetic (PK) approach to estimate CYP2C9 activity in healthy adults. In 6 previously published studies, a single oral dose of warfarin 10 mg was administered alone or with a CYP2C9 inducer to 100 healthy adults. S-warfarin concentrations were obtained from adults during conditions when subjects were not on any prescribed medications. A population PK model was developed using non-linear mixed effects modeling. Limited sampling models (LSMs) using single- or 2-timepoint concentrations were compared with full PK profiles from intense sampling using empiric Bayesian post hoc estimations of S-warfarin AUC derived from the population PK model. Preset criterion for LSM selection and validation were a correlation coefficient (R2) >0.9, relative percent mean prediction error (%MPE) >−5 to |
Databáze: | OpenAIRE |
Externí odkaz: |