An alternative two stage method via the EM-algorithm for the estimation of population pharmacokinetic parameters.

There has been a considerable increase in popularity of the NONMEM method as a technique for estimating population pharmacokinetic parameters. The authors present another approach to population pharmacokinetic analysis, the alternative two stage method (ATS). ATS uses the EM-algorithm for maximizing the likelihood of variance components. The performance of ATS was compared with the NONMEM method on a microcomputer. Simulation studies showed that the precision and accuracy of estimates obtained with ATS were comparable to the NONMEM method, however, the computation time, dependences on initial estimates and convergence properties were somewhat different. ATS could be a valuable alternative to the NONMEM method for estimating population pharmacokinetic parameters in some cases.