Experimental design and efficient parameter estimation in population pharmacokinetics

摘要: A computer simulation technique used to evaluate the influence of several aspects sampling designs on efficiency population pharmacokinetic parameter estimation is described. Although simulations are restricted one-compartment one-exponential model, they provide basis for a discussion structural involved in designing study. These include number subjects required, samples per subject, and timing these samples. Parameter estimates obtained from different schedules based two- three-point evaluated terms accuracy precision. simulated data sets noise both inter- intraindividual variability. The results show that fixed-effect parameters (mean clearance mean volume distribution) this simple model efficiently estimated most when two or three points used, but random-effect (describing variability) inaccurate imprecise only used. This drawback was remedied by increasing individual three.