Clinical pharmacology of morphine in infants and children

Morphine is used to treat pain, for treatment of opioid dependence, and neonatal abstinence syndrome. Morphine is modestly absorbed from the gastrointestinal tract whereas after rectal administration, by intranasal or buccal application morphine is well absorbed. Morphine is eliminated by glomerular filtration and by conjugation with glucuronic acid; morphine-3-glucurinide and morphine-6-glucurinide are the main metabolites and the last has analgesic effect. In infants, morphine is used to treat severe or sustained pain, sedation, and pain relief. In children, morphine is used to control pain and morphine may be administered by subcutaneous or intravenous injection, orally, by rectum, or by continuous subcutaneous infusion and morphine dose varies according to the child age. Morphine has been found efficacy and safe in infants and children but may induce adverse-effects. The effects caused by morphine and the treatment with morphine have been studied in infants and children. In newborns, morphine elimination half-life ranges from 7.7 to 13.5 hours and decreases with infant maturation. In newborns, infants and children, the total body clearance of morphine ranges from 14.5 to 71.1 L/h/70kg and increases with infant maturation and child development. Morphine is transported in the human brain, poorly crosses the human placenta and accumulates in breast-milk. The aim of this study is to review the published data on morphine dosing, efficacy and safety, effects, adverse-effects, pharmacokinetics, metabolism, drug interaction, treatment, transport into human brain of infants and children and morphine transfer across the human placenta and migration into the breast-milk.