Application of Physiologically Based Pharmacokinetic Modeling to Predict Pharmacokinetics in Healthy Japanese Subjects.

ABSTRACT: Pharmacokinetics (PKs) in Japanese healthy subjects were simulated for nine compounds using physiologically based PK (PBPK) models parameterized with physicochemical properties, preclinical absorption, distribution, metabolism, and excretion (ADME) data, and clinical PK data from non-Japanese subjects. For each dosing regimen, 100 virtual trials were simulated and predicted/observed ratios for peak plasma concentration (C_max ) and area under the curve (AUC) were calculated. As qualification criteria, it was prespecified that >80% of simulated trials should demonstrate ratios to observed data ranging from 0.5-2.0. Across all compounds and dose regimens studied, 93% of simulated C_max values in Japanese subjects fulfilled the criteria. Similarly, for AUC, 77% of single-d

SUBMITTER: Matsumoto Y 

PROVIDER: S-EPMC6587435 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature