Prenatal and neonatal drug metabolism in man

Summary

Drug oxidations are catalyzed by the liver microsomal fraction of human fetuses but not by fetal livers from most experimental animals. In contrast, glucuronidation of some substrates is catalyzed by the rat fetal liver in late gestation but not in the human fetal liver. The deficient human fetal glucuronidation seems to be compensated for by early development of sulfation activity. The inconsistency of the results from animal fetuses and human fetuses shows that animal data have little relevance for the human fetus. No generalized statements can be made about drug disposition in the newborn infant as compared to adults. Although most drugs that are oxidized have prolonged plasma half-lives in the neonatal period there are examples of drugs with half-lives similar to, or even shorter than, the average half-lives in adults. Oxazepam is conjugated with glucuronic acid in adults. The neonatal plasma half-life of this drug is considerably prolonged. This is true also for its conjugate as would be expected from the immature renal function in newborns. Adequate pharmacokinetic information is a prerequisite for rational and safe drug treatment in the neonatal period.