Renal tubular secretion of meperidine by the fetal lamb

We have determined the renal clearance of meperidine and inulin simultaneously under steady-state conditions by using the chronic fetal lamb preparation. Meperidine was infused at a constant rate of 3.2 mg/min into the maternal vena cava, and [14C]inulin was infused at a constant rate of 0.22 muCi/min into the fetal vena cava. Total fetal urine output was collected for three consecutive 15-min intervals, and fetal blood was sampled at the midpoint of each urine collection. The mean meperidine clearance in 12 studies was 12.04 +/- 2.90 (S.E.) ml/min, whereas mean inulin clearance was 2.48 +/- 0.35 (S.E.) ml/min. In all but one animal, the ratio of meperidine clearance to inulin clearance is greater than one, indicating tubular secretion of meperidine. The results show that there is a negative relationship between meperidine clearance and urine pH, but there is no relationship between meperidine clearance and gestational age or urine flow rate. These results suggest that meperidine is secreted across the renal tubules by "ion trapping."