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

To explore the pharmacokinetics of oral morphine and the potential effect of pharmacogenetics on efficacy and safety in children.

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.

A total of 13 children received a single dose of oral morphine 0.5 mg/kg. For morphine, M6G, and M3G, median T_max was 52.5, 90, and 90 min, respectively. Median C_max reached 14.07, 53.64, and 309.63 ng/mL, respectively. Median t_1/2 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.

Oral morphine's active metabolites have a longer t_1/2 and an OPMR1 SNP rs563649 may underlie variability in efficacy and safety. Clinical Trials Registration: clinicaltrials.gov NCT01690780.