PT - JOURNAL ARTICLE AU - Tatiana Nanovskaya AU - Sujal Deshmukh AU - Monica Brooks AU - Mahmoud S. Ahmed TI - Transplacental Transfer and Metabolism of Buprenorphine AID - 10.1124/jpet.300.1.26 DP - 2002 Jan 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 26--33 VI - 300 IP - 1 4099 - http://jpet.aspetjournals.org/content/300/1/26.short 4100 - http://jpet.aspetjournals.org/content/300/1/26.full SO - J Pharmacol Exp Ther2002 Jan 01; 300 AB - Information on the direct and indirect effects of buprenorphine (BUP) on the fetus is essential for determining its potential for treatment of the pregnant opiate addict. The goal of this investigation is to determine the transplacental transfer of BUP to the fetal circulation, its metabolism, and effects on the tissue. The technique of dual perfusion of placental lobule is used. The range of BUP concentrations investigated included its peak plasma levels (10 ng/ml) in patients under treatment. A biphasic decline in concentration of the drug in the maternal circulation was observed, initially rapid then slow. During the initial (60 min), the tissue sequestered most of BUP resulting in a low (<10%) transplacental transfer of the drug to the fetal circulation. The concentration ratios of the drug in tissue/maternal and tissue/fetal were 13 ± 6.5 and 27.4 ± 0.4. The drug sequestered did not have any adverse effects on placental tissue viability and functional parameters. Less than 5% of the perfused BUP was metabolized to norbuprenorphine during the 4 h of perfusion and the metabolite was distributed between the tissue, maternal, and fetal circulations. Taken together, these data suggest that the therapeutic levels of BUP in the maternal circulation may have no indirect effects (via the placenta) on the fetus. The observed low transplacental transfer of BUP to the fetal circuit may explain the moderate/absence of neonatal withdrawal in the limited number of reports on mothers treated with the drug during pregnancy. BUPbuprenorphineCYPcytochrome P450hCGhuman chorionic gonadotropinAPantipyrineAUCarea under the concentration-time curvenorBUPnorbuprenorphineHPLChigh-performance liquid chromatography