Clinical Pharmacology of Methadone in Infants and Children

Methadone is a long-acting µ opioid receptor agonist with pharmacological properties qualitatively similar to those of morphine, is a racemate, consists in R-methadone and S-methadone and the analgesic activity is due to R-methadone. In infants, the initial oral dose of methadone is 100 µg/kg 4 times-daily. In children, methadone is given by sublingual application, orally, intramuscularly, or intravenously and the dose of methadone varies according to the child body-weight. Methadone has been found efficacy and safe in infants and children but may induce toxicity. Methadone is metabolized into inactive metabolites by different cytochromes P450, the main metabolite is 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and females catalyse the formation of EDDP at higher activity than males. The pharmacokinetics of methadone have been studied in infants following oral administration and methadone is rapidly absorbed. The pharmacokinetics of R-methadone and S-methadone have been studied in children in adult patients and in adolescents and the pharmacokinetic parameters of R-methadone are different from those of S-methadone indicating that the disposition of methadone is stereoselective. Methadone interacts with drugs and the treatment and trials with methadone have been reviewed in infants and children. Methadone causes different effects in the human brain, poorly crosses the human placenta, and migrates into the breast-milk in significant amounts. The aim of this study is to review the methadone dosing, efficacy and safely, pharmacokinetics, treatment, and trials in infants and children, and methadone toxicity, metabolism, interaction with drugs, effects on human brain, placental transfer, and migration into breast-milk.