Pharmacokinetics of Morphine and Its Metabolites in Infants and Young Children After Congenital Heart Surgery

The AAPS Journal
Mohammed H ElkomyGregory B Hammer

Abstract

The objective of this study was to characterize morphine glucuronidation in infants and children following cardiac surgery for possible treatment individualization in this population. Twenty children aged 3 days to 6 years, admitted to the cardiovascular intensive care unit after congenital heart surgery, received an intravenous (IV) loading dose of morphine (0.15 mg/kg) followed by subsequent intermittent IV bolus doses based on a validated pain scale. Plasma samples were collected over 6 h after the loading dose and randomly after follow-up doses to measure morphine and its major metabolite concentrations. A population pharmacokinetic model was developed with the non-linear mixed effects software NONMEM. Parent disposition was adequately described by a linear two-compartment model. Effect of growth (size and maturation) on morphine parameters was accounted for by allometric body weight-based models. An intermediate compartment with Emax model best characterized glucuronide concentrations. Glomerular filtration rate was identified as a significant predictor of glucuronide formation time delay and maximum concentrations. Clearance of morphine in children with congenital heart disease is comparable to that reported in children w...Continue Reading

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Citations

May 27, 2016·Journal of Clinical Pharmacology·Adam FrymoyerKrisa P Van Meurs
Apr 26, 2018·World Journal for Pediatric & Congenital Heart Surgery·Uri Pollak, Alain Serraf
Jan 25, 2018·Expert Opinion on Drug Metabolism & Toxicology·Tamara Van DongeKarel Allegaert

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