Oral morphine pharmacokinetics in healthy children and the effect of genetic polymorphisms: An exploratory study

ABSTRACT Objectives To explore the pharmacokinetics of oral morphine and the potential effect of pharmacogenetics on efficacy and safety in children. Methods Serial blood samples were obtained from healthy children aged 5–17 years. We determined morphine, morphine-6-glucoronide (M6G) and morphine-3-glucoronide (M3G) concentrations and pharmacokinetic parameters. We performed genotyping and collected pain scores. Results A total of 13 children received a single dose of oral morphine 0.5 mg/kg. For morphine, M6G, and M3G, median Tmax was 52.5, 90, and 90 min, respectively. Median Cmax reached 14.07, 53.64, and 309.63 ng/mL, respectively. Median t1/2 was 74.96, 170.73, and 149.45 min, respectively. Median area under the curve was 1757.71, 3290.83, and 43618.97 ng*h/mL, respectively. A single nucleotide polymorphism rs563649 on the OPRMI gene locus was associated with reduced receptor efficiency in one patient reporting an increase in pain. Conclusions Oral morphine’s active metabolites have a longer t1/2 and an OPMR1 SNP rs563649 may underlie variability in efficacy and safety. Clinical Trials Registration: clinicaltrials.gov NCT01690780.