ABCC3 and OCT1 genotypes influence pharmacokinetics of morphine in children.

ABSTRACT:

Aim

Large interindividual variability in morphine pharmacokinetics could contribute to variability in morphine analgesia and adverse events.

Methods

Influence of weight, genetic polymorphisms, race and sex on morphine clearance and metabolite formation from 220 children undergoing outpatient adenotonsillectomy was studied. A nonlinear mixed effects model was developed in NONMEM to describe morphine and morphine glucuronide pharmacokinetics.

Results

Children with ABCC3 -211C>T polymorphism C/C genotype had significantly higher levels of morphine-6-glucuronide and morphine-3-glucuronide formation (∼40%) than C/T+T/T genotypes (p < 0.05). In this extended cohort similar to our earlier report, OCT1 homozygous genotypes (n = 13, OCT1*2-*5/*2-*5) had lower morphine clearanc

SUBMITTER: Venkatasubramanian R 

PROVIDER: S-EPMC4190075 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature