Szeto H H, Clapp J F, Larrow R W, Inturrisi C E, Mann L I
J Pharmacol Exp Ther. 1980 May;213(2):346-9.
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."
我们通过使用慢性胎羊制备方法，在稳态条件下同时测定了哌替啶和菊粉的肾清除率。哌替啶以3.2毫克/分钟的恒定速率注入母体腔静脉，[14C]菊粉以0.22微居里/分钟的恒定速率注入胎儿腔静脉。连续三个15分钟时间段收集胎儿总尿量，并在每次尿液收集的中点采集胎儿血液样本。12项研究中哌替啶的平均清除率为12.04±2.90（标准误）毫升/分钟，而菊粉的平均清除率为2.48±0.35（标准误）毫升/分钟。除一只动物外，所有动物的哌替啶清除率与菊粉清除率之比均大于1，表明哌替啶存在肾小管分泌。结果表明，哌替啶清除率与尿液pH值呈负相关，但哌替啶清除率与胎龄或尿流率之间无相关性。这些结果提示，哌替啶是通过“离子捕获”作用经肾小管分泌的。
