Prenatal administration of buprenorphine using the osmotic minipump: a preliminary study of maternal and offspring toxicity and growth in the rat.
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.
Hutchings
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DE
New York State Psychiatric Institute, Department of Developmental Psychobiology, New York, NY 10032, USA.
Zmitrovich
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AC
Hamowy
A S
AS
Liu
P Y
PY
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002047:Buprenorphine / Q000008:administration & dosage / Q000633:toxicity*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D006801:Humans; D015918:Infusion Pumps, Implantable; D008297:Male; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D009294:Narcotics / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar
D009292:Narcotic Antagonists; D009294:Narcotics; D002047:Buprenorphine