Characterization of Contributing Factors to Variability in Morphine Clearance Through PBPK Modeling Implemented With OCT1 Transporter.

ABSTRACT: Morphine shows large interindividual variability in its pharmacokinetics; however, the cause of this has not been fully addressed. The variability in morphine disposition is considered to be due to a combination of pharmacogenetic and physiological determinants related to morphine disposition. We previously reported the effect of organic cation transporter (OCT1) genotype on morphine disposition in pediatric patients. To further explore the underlying mechanisms for variability arising from relevant determinants, including OCT1, a physiologically based pharmacokinetic (PBPK) model of morphine was developed. The PBPK model predicted morphine concentration-time profiles well, in both adults and children. Almost all of the observed morphine clearances in pediatric patients fell within a twofo

SUBMITTER: Emoto C 

PROVIDER: S-EPMC5321811 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature