Meperidine pharmacokinetics in the maternal-fetal unit
Meperidine pharmacokinetics in the maternal-fetal unit were evaluated by use of the chronic pregnant ewe preparation. After maternal administration (i.v. 2.5 mg/kg), meperidine appears in fetal plasma within 2 min at a level approaching that in maternal plasma. The maternal t(.5β) is 20.4 ± 2.6 min and the fetal t(.5β) is 22.6 ± 2.4 min. Compared to the i.v. dose kinetics, the rate and amount of meperidine transferred from mother to fetus is decreased after intramuscular administration. After the administration of normeperidine to the mother, fetal normeperidine plasma levels peak at 5 min, and a decline at a slower rate than maternal levels (maternal t(.5β) is 43.3 min; fetal t(.5β) is 79.3 min). When meperidine is administered i.v. the fetus, the drug appears in maternal plasma within 2 min and peaks at 5 min. Administration of meperidine directly into amniotic fluid results in the rapid appearance of drug in maternal plasma, and subsequently in fetal plasma. After a continuous infusion of meperidine (0.06 mg/kg/min) to the mother, steady state is achieved in both maternal and fetal plasma within 60 min. At steady state, the fetal/maternal plasma meperidine concentration ratio is equal to 0.3. When differences between maternal and fetal plasma protein binding and degree of ionization are taken into account, the recalculated steady-state concentration ratio is 0.38. The authors propose that meperidine confers on the maternal-fetal unit the characteristics of a two-compartment open model with elimination from both maternal and fetal compartments. This model suggests that the elimination by the fetus makes an important contribution to the disposition of meperidine.