title: Optimal design of perturbations for individual two-compartment pharmacokinetic analysis.
abstract: We consider the optimal design of pharmacokinetic studies in patients that receive intermittent hemodialysis and intravenous antibiotic. Hemodialysis perturbs the pharmacokinetic system, providing additional opportunity for study. Designs that allocate measurements to occur exclusively during hemodialysis are shown to be viable alternatives to conventional designs, where all measurements occur outside of hemodialysis. Furthermore, hybrid designs with both conventional and intradialytic measurements have nearly double the efficiency of conventional designs. Convex optimal design and Monte Carlo techniques were used to simultaneously optimize hemodialysis event characteristics and sampling times, accounting for population pharmacokinetic heterogeneity. We also present several related methodological innovations.
authors.affiliation: a Department of Biostatistics , Vanderbilt University , Nashville , Tennessee , USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Shotwell
authors.affiliation: a Department of Biostatistics , Vanderbilt University , Nashville , Tennessee , USA.
authors.forename: Minchun
authors.initials: M
authors.lastname: Zhou
authors.affiliation: b Department of Medicine , Vanderbilt University , Nashville , Tennessee , USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Fissell
mesh_terms: D061605:Administration, Intravenous; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D015233:Models, Statistical; D009010:Monte Carlo Method; D006435:Renal Dialysis
chemical_list: D000900:Anti-Bacterial Agents
keywords: Challenge response; hemodialysis; optimal design; pharmacokinetic; piperacillin; simulation; two-compartment model