Recommended use of morphine in neonates, infants and children based on a literature review: Part 1--Pharmacokinetics.

The English language literature has been reviewed in order to evaluate the present knowledge on morphine's metabolism and pharmacokinetics in children. The majority of preterm neonates are capable of glucuronidating morphine, but birth weight; gestational and postnatal age influence the glucuronidation capability. Term neonates, infants, and children are able to produce morphine glucuronides. For the reported pharmacokinetics parameters a meta-analysis was made; volume of distribution, estimated to be 2.8 +/- 2.6 l.kg-1, seems to be regardless of age, while half-life and clearance were found to be related to age. Half-life was estimated to be 9.0 +/- 3.4 h in pre-term neonates, 6.5 +/- 2.8 h in term neonates aged 0-57 days, and 2.0 +/- 1.8 h for infants and children aged 11 days to 15 years. Clearance was estimated to be 2.2 +/- 0.7 ml.min-1.kg-1 for preterm neonates, 8.1 +/- 3.2 ml.min-1.kg-1 in term neonates aged 0-57 days, and 23.6 +/- 8.5 ml.min-1.kg-1 in infants and children more than 11 days old.