URINARY-EXCRETION OF MEPERIDINE BY THE FETAL LAMB

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Abstract
The renal excretion of meperidine by the fetus was determined in 5 chronic unanesthesized fetal lamb preprations. Chronic indwelling catheters were implanted in the maternal aorta and vena cava, the fetal aorta, amniotic sac and allantoic sac. Via laparotomy 2 catheters were implanted in the fetal bladder. The urachus and urethra were ligated. After i.v. administration of 2.5 mg/kg to the mother meperidine rapidly appears in fetal urine. Of the maternal dose .apprx. 0.2-.05% was excreted into fetal urine as unchanged meperidine in 300 min. The elimination half-life of meperidine in the fetus is 32.6 .+-. 3.7 min when calculated from the urinary excretion rates, and 28.6 .+-. 3.9 min when estimated from the plasma decay curve. The renal clearance of meperidine by the fetus ranged from 2.8-16.7 ml/min. Although the urachus and urethra were ligated meperidine was found in samples of amniotic and allantoic fluid indicating that the drug can diffuse across the placental membranes from the mother into the fluids. Apparently renal elimination of meperidine is a route of drug elimination by the fetus. A pharmacokinetic model that describes the disposition of meperidine in the maternal-fetal unit by use of a 2-compartment open model with elimination from both maternal and fetal compartments was supported.