ABCC3 and OCT1 genotypes influence pharmacokinetics of morphine in children.

Article Details


Venkatasubramanian R, Fukuda T, Niu J, Mizuno T, Chidambaran V, Vinks AA, Sadhasivam S

ABCC3 and OCT1 genotypes influence pharmacokinetics of morphine in children.

Pharmacogenomics. 2014 Jul;15(10):1297-309. doi: 10.2217/pgs.14.99.

PubMed ID
25155932 [ View in PubMed

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 ( approximately 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 ( approximately 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.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
CodeineSolute carrier family 22 member 1ProteinHumans