• Raja Venkatasubramanian, Tsuyoshi Fukuda, Jing Niu, Tomoyuki Mizuno, Vidya Chidambaran, Alexander A Vinks, and Senthilkumar Sadhasivam.
• Department of Anesthesia, Cincinnati Children's Hospital Medical Center; 3333 Burnet Avenue, MLC 2001, Cincinnati, OH 45229, USA.
• Pharmacogenomics. 2014 Jul 1; 15 (10): 1297-309.

AimLarge interindividual variability in morphine pharmacokinetics could contribute to variability in morphine analgesia and adverse events.MethodsInfluence 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.ResultsChildren 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.ConclusionOur data suggest that besides bodyweight, OCT1 and ABCC3 genotypes play a significant role in the pharmacokinetics of intravenous morphine and its metabolites in children.

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