The Importance of Modeling Interoccasion Variability in Population Pharmacokinetic Analyses

摘要: Individual pharmacokinetic parameters may change randomly between study occasions. Analysis of simulated data with NONMEM shows that ignoring such interoccasion variability (IOV) result in biased population parameter estimates. Particular affected and the extent to which they are depend on design magnitude IOV interindividual variability. Neglecting also results a high incidence statistically significant spurious period effects. Perhaps most important, can lead falsely optimistic impression potential value therapeutic drug monitoring. A model incorporating was developed its performance presence absence evaluated. The performs well respect both selection estimation all circumstances studied. two real examples using this reveals for drugs supports simulation findings case is ignored: predictable biases occur estimates previously nonexistent effects found.