Intersubject Variability in Pharmacokinetics and Subject Characteristics in Phase I Studies

• Activity Number: 192
• Type: Contributed
• Date/Time: Monday, July 30, 2012 : 10:30 AM to 12:20 PM
• Sponsor: Section for Statistical Programmers and Analysts
• Author(s): Peng Chai*+ and Chun Feng and Xiaopeng Li
• Companies: Celerion and Celerion and Celerion
• Keywords: Mixed-effects model ; pharmacokinetics ; intersubject variability ; subject characteristics

Abstract

Pharmacokinetic (PK) and safety results of Phase 1 studies are assessed by pharmacokineticist and medical writer respectively with the statistician working on PK statistical modeling. The statistician can do more through analysis of intersubject variability in PK and subject characteristics. High intersubject variability in PK indicates variation in drug absorption, distribution, or elimination across subjects. Examination of subject characteristics predictive for differences in PK is then desirable. When a subject's PK responses are repeatedly measured, mixed-effects modeling can provide estimation of fixed-effects parameters, intersubject variability, and residual random effects (including intrasubject variability). After mixed ANOVA model, more interest is often on intrasubject CV for estimating power. The intersubject CV can also be derived. A high value (e.g., 30% or more) should lead to further study. For example, regression analysis or data visualization on laboratory tests for liver and renal functions can link PK and these subject characteristics. Thus, without a full population PK study, the statistician can perform some quick analyses on the drug's therapeutic potential.