ABCC3 and OCT1 genotypes influence pharmacokinetics of morphine in children
Raja Venkatasubramanian1, Tsuyoshi Fukuda, Jing Niu
1Department of Anesthesia, Cincinnati Children's Hospital Medical Center; 3333 Burnet Avenue, MLC 2001, Cincinnati, OH 45229, USA.
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 clearance (14%; p = 0.06), and in addition complementing lower metabolite formation (∼39%) was observed. ABCB1 3435C>T TT genotype children had lower levels of morphine-3-glucuronide formation though no effect was observed on morphine and morphine-6-glucuronide pharmacokinetics.
Conclusion:
Our data suggest that besides bodyweight, OCT1 and ABCC3 genotypes play a significant role in the pharmacokinetics of intravenous morphine and its metabolites in children.
More Related Videos
Related Concept Videos
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacokinetics in Pediatric Patients: Drug Metabolism
Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes


