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使用渗透微型泵进行丁丙诺啡的产前给药:对大鼠母体及子代毒性和生长的初步研究

Prenatal administration of buprenorphine using the osmotic minipump: a preliminary study of maternal and offspring toxicity and growth in the rat.

作者信息

Hutchings D E, Zmitrovich A C, Hamowy A S, Liu P Y

机构信息

New York State Psychiatric Institute, Department of Developmental Psychobiology, New York, NY 10032, USA.

出版信息

Neurotoxicol Teratol. 1995 Jul-Aug;17(4):419-23. doi: 10.1016/0892-0362(94)00079-s.

Abstract

Buprenorphine, an opioid with mixed agonist-antagonist properties, is gaining new attention as an effective pharmacotherapy for opioid and possibly cocaine abuse. With a view to its consideration for use with pregnant clients and because so little is know of its potential developmental toxicity, we have carried out this preliminary study. Three doses of buprenorphine (BUP) were administered by osmotic minipump from day 8 of gestation through parturition. In addition to 0.3, 1.0, and 3.0 mg/kg/day of BUP, a vehicle control group received sterile water via minipump and a nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. BUP produced a dose response reduction in maternal water intake but had no effect on maternal weight gain, the frequency of resorptions, or birthweight. BUP had no effect on perinatal mortality and produced inconsistent effects on postnatal growth. The unique chemical and pharmacological properties of this compound, especially its bell-shaped or asymptotic dose response effects, are discussed with respect to the development of an adequate animal model to evaluate neurobehavioral effects and assess its safety for use during pregnancy.

摘要

丁丙诺啡是一种具有混合激动-拮抗特性的阿片类药物,作为一种治疗阿片类药物滥用甚至可能是可卡因滥用的有效药物疗法正受到新的关注。鉴于考虑将其用于孕妇,且对其潜在发育毒性了解甚少,我们开展了这项初步研究。从妊娠第8天至分娩,通过渗透微型泵给予三种剂量的丁丙诺啡(BUP)。除了每天给予0.3、1.0和3.0mg/kg的BUP外,一个溶媒对照组通过微型泵接受无菌水,一个未治疗对照组在妊娠期间不做处理。所有接受治疗和对照的窝仔在出生时寄养给未治疗的母鼠。BUP使母鼠饮水量呈剂量反应性减少,但对母鼠体重增加、吸收频率或出生体重没有影响。BUP对围产期死亡率没有影响,对出生后生长的影响也不一致。就建立一个合适的动物模型以评估神经行为效应并评估其在孕期使用的安全性而言,讨论了该化合物独特的化学和药理学特性,尤其是其钟形或渐近性剂量反应效应。

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