Influence of Inter-Animal Variability on the Estimation of Population Pharmacokinetic Parameters in Preclinical Studies

Abstract

AbstractSingle response population (1 sample / animal) simulation studies were carried out (assuming a 1 compartment model) to investigate the influence of inter-animal variability (in clearance (σCl) and volume (σv)) on the estimation of population pharmacokinetic parameters. NONMEM was used for parameter estimation. Individual and joint confidence intervals coverage for parameter estimates were computed to reveal the influence of bias and standard error (SE) on interval estimates. The coverage of interval estimates, percent prediction error and correlation analysis were used to judge the efficiency of parameter estimation. The efficiency of estimation of Cl and V was good, on average, irrespective of the values of σCl and σv Estimates of σCl and σv were biased and imprecise. Small biases and high precision resulted in good confidence intervals coverage for Cl and V. SE was the major determinant of confidence intervals coverage for the random effect parameters, σCl and σv and the joint confidence interva...