ABCC3 and OCT1 genotypes influence pharmacokinetics of morphine in children.

Article Details

Citation

Copy to clipboard

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

]

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 ( 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

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Codeine	Solute carrier family 22 member 1	Protein	Humans	Unknown	Substrate Inhibitor	Details