Szeto H H, Kaiko R F, Clapp J F, Larrow R W, Mann L I, Inturrisi C E
J Pharmacol Exp Ther. 1979 May;209(2):244-8.
The renal excretion of meperidine by the fetus was determined in five chronic, unanesthesized fetal lamb preparations. Chronic indwelling catheters were implanted in the maternal aorta and vena cava, the fetal aorta, amniotic sac and allantoic sac. Via laparotomy, two catheters were implanted in the fetal bladder; the urachus and urethra were ligated. After intravenous administration of 2.5 mg/kg to the mother, meperidine rapidly appears in fetal urine. Approximately 0.02 to 0.05% of the maternal dose 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 to 16.7 ml/min. Although the urachus and urethra were ligated, meperidine is found in samples of amniotic and allantoic fluid, indicating that the drug can diffuse across the placental membranes from the mother into these fluids. We have demonstrated that renal elimination of meperidine is a route of drug elimination by the fetus. These data support a pharmacokinetic model that describes the disposition of meperidine in the maternal-fetal unit by use of a two-compartment open model with elimination from both maternal and fetal compartments.
在五个慢性、未麻醉的胎羊实验制剂中测定了胎儿对哌替啶的肾排泄情况。将慢性留置导管植入母羊的主动脉和腔静脉、胎儿的主动脉、羊膜囊和尿囊。通过剖腹术,将两根导管植入胎儿膀胱;结扎脐尿管和尿道。给母体静脉注射2.5mg/kg哌替啶后,哌替啶迅速出现在胎儿尿液中。在300分钟内,约0.02%至0.05%的母体剂量以未改变的哌替啶形式排泄到胎儿尿液中。根据尿排泄率计算,胎儿体内哌替啶的消除半衰期为32.6±3.7分钟,根据血浆衰减曲线估计为28.6±3.9分钟。胎儿对哌替啶的肾清除率为2.8至16.7ml/分钟。尽管结扎了脐尿管和尿道,但在羊水和尿囊液样本中发现了哌替啶,这表明该药物可从母体通过胎盘膜扩散到这些液体中。我们已经证明,哌替啶的肾排泄是胎儿药物消除的一条途径。这些数据支持了一个药代动力学模型,该模型通过使用一个双室开放模型来描述哌替啶在母胎单元中的处置情况,该模型同时考虑了母体和胎儿隔室的消除。