Morrison J C, Martin J N, Christie R J, Martin R W, Hess L W, Wiser W L, Bucovaz E T, Stafford D T, Anderson W H
Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson 39216-4505.
J Perinatol. 1988 Winter;8(1):24-6.
Previous work has shown that both meperidine and normeperidine are transferred across the placenta to the fetus. Little is known in primates, however, about the tissue deposition of these compounds. Four pregnant, dated rhesus monkeys within one week of term were anesthetized for cesarean delivery. An equal mixture of meperidine and normeperidine was administered as an intravenous bolus 10 minutes before delivery (1.25 mg/kg). The infants were then sacrificed at 20 minutes after birth and the concentration of the compounds in various organ systems were analyzed by gas-liquid chromatography and mass spectroscopy (GLC-MS). The infant serum 20 minutes after delivery revealed a meperidine concentration of 2.23 micrograms/ml and a normeperidine level of 0.67 micrograms/ml (3:1). In contrast, the tissues analyzed showed a much higher concentration of the metabolite in the liver (1:7), gallbladder (1:3), and brain (1:2). Other tissues, such as muscle and kidney, demonstrated equal levels of the two compounds. The authors conclude that normeperidine is quickly transferred to fetal tissues and to a greater degree than the parent compound in certain organs. The increased distribution, particularly in the brain, could account for the toxic actions in the cerebrum of the derivatives of meperidine.
先前的研究表明,哌替啶和去甲哌替啶均可经胎盘转运至胎儿体内。然而,在灵长类动物中,关于这些化合物在组织中的沉积情况却知之甚少。选取了4只足月前一周的怀孕恒河猴,对其进行剖宫产麻醉。在分娩前10分钟静脉推注(1.25毫克/千克)哌替啶和去甲哌替啶的等量混合物。然后在婴儿出生后20分钟将其处死,通过气液色谱法和质谱法(GLC-MS)分析各器官系统中这些化合物的浓度。分娩后20分钟时,婴儿血清中哌替啶浓度为2.23微克/毫升,去甲哌替啶水平为0.67微克/毫升(3:1)。相比之下,所分析的组织中,肝脏(1:7)、胆囊(1:3)和大脑(1:2)中的代谢产物浓度要高得多。其他组织,如肌肉和肾脏,两种化合物的水平相当。作者得出结论,去甲哌替啶能迅速转运至胎儿组织,且在某些器官中的转运程度高于母体化合物。其分布增加,尤其是在大脑中的分布增加,可能是哌替啶衍生物对大脑产生毒性作用的原因。