title: A new method to explore the distribution of interindividual random effects in non-linear mixed effects models.
abstract: This article presents a new approach for exploring the distribution of interindividual random effects in nonlinear mixed effect models. The approach introduces a spline function, which transforms an assumed normally distributed interindividual random effect to an arbitrary distribution approximating that of the data. The performance of this tool is illustrated using simulated pharmacokinetic data with non-normally distributed random effects. Results of the analyses of two real kinetic data sets are also presented.
authors.affiliation: Department of Pharmacy and Pharmaceutical Chemistry, University of California San Francisco 94143, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Fattinger
authors.forename: L B
authors.initials: LB
authors.lastname: Sheiner
authors.forename: D
authors.initials: D
authors.lastname: Verotta
mesh_terms: D001699:Biometry / Q000379:methods*; D006348:Cardiac Surgical Procedures; D003402:Creatine Kinase / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D007527:Isoenzymes; D017711:Nonlinear Dynamics; D010599:Pharmacokinetics; D010634:Phenobarbital / Q000493:pharmacokinetics
chemical_list: D007527:Isoenzymes; D003402:Creatine Kinase; D010634:Phenobarbital