Flip-flop pharmacokinetics--delivering a reversal of disposition: challenges and opportunities during drug development.

ABSTRACT: Flip-flop pharmacokinetics is a phenomenon often encountered with extravascularly administered drugs. Occurrence of flip-flop spans preclinical to human studies. The purpose of this article is to analyze both the pharmacokinetic interpretation errors and opportunities underlying the presence of flip-flop pharmacokinetics during drug development. Flip-flop occurs when the rate of absorption is slower than the rate of elimination. If it is not recognized, it can create difficulties in the acquisition and interpretation of pharmacokinetic parameters. When flip-flop is expected or discovered, a longer duration of sampling may be necessary in order to avoid overestimation of fraction of dose absorbed. Common culprits of flip-flop disposition are modified dosage formulations; however, formulatio

SUBMITTER: Yanez JA 

PROVIDER: S-EPMC3152312 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature