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.

KEYWORDS:

• Challenge response
• hemodialysis
• optimal design
• pharmacokinetic
• piperacillin
• simulation
• two-compartment model

Acknowledgments

We acknowledge the support of John P. Wikswo and the Vanderbilt Institute for Integrative Biosystems Research and Education.

Funding

This work was partially supported by NIH/NHLBI grant number 1R01HL118392-01.

Supplemental material

Supplemental data for this article can be accessed at http://www.tandfonline.com/lbps.

Additional information

Funding

This work was partially supported by NIH/NHLBI grant number 1R01HL118392-01.