| Objective. The common belief in pharmacokinetics is that drug clearance is linearly related to renal function. For those drugs excreted by the kidney, the pharmacokinetics of individual drugs in patients with impaired renal function have been well studied using this assumption. Our objective was to determine the optimal study design to examine a linear relationship between total body drug clearance and renal function. Methods. Computer simulation was applied to investigate the impact of sample size and randomly added error on the determination of a statistically significant linear relationship between renal function and drug clearance. Conclusion. The traditional study design recommended by the FDA guidance for PK studies in patients with renal impairment is adequate for detecting a linear relationship given sufficient sample size and if the true relationship is linear. However, when the actual relationship is nonlinear, a linear relationship or no relationship between renal function and drug clearance might be incorrectly predicted using the traditional study design. To optimize the study design, not only linear but also nonlinear relationships should be explored in the data analysis. (Abstract shortened by UMI.)... |
