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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on April 3, 2003; DOI: 10.1124/jpet.103.050690

0022-3565/03/3061-205-212$20.00
JPET 306:205-212, 2003
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ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Transfer of L-{alpha}-Acetylmethadol (LAAM) and L-{alpha}-Acetyl-N-normethadol (norLAAM) by the Perfused Human Placental Lobule

Tatiana N. Nanovskaya, Sujal V. Deshmukh, Rachel Miles, Steve Burmaster, and Mahmoud S. Ahmed

Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas (T.N.N., S.V.D., M.S.A.); Kansas City School of Pharmacy, University of Missouri, Kansas City, MO (R.M.); and Quintiles, Inc., Kansas City, MO (S.B.)

The agonists buprenorphine and L-{alpha}-acetylmethadol (LAAM) were introduced as alternatives to methadone for treatment of the adult opiate addict. The direct and indirect effects of these drugs on normal fetal growth and development are currently under investigation in our laboratory. The goal of this report is to provide part of the data necessary to assess the safety of LAAM in treatment of the pregnant opiate addict. To achieve this goal, the technique of dual perfusion of placental lobule was utilized to determine the kinetics for transplacental transfer of LAAM and its effects on the viability and functional parameters of the tissue. LAAM is rapidly metabolized to the pharmacologically active norLAAM that was also included in this investigation. The two opiates were transfused at their plasma levels in patients under treatment, a concentration of 35 ng/ml. The drugs exhibited similar pharmacokinetic profiles, characterized by an initial phase of distribution into placental tissue followed by their low transfer to the fetal circuit. During the 4-h experimental period, the transfused tissue retained significant amounts of LAAM and norLAAM, and neither drug was metabolized. LAAM did not affect placental tissue viability and functional parameters. However, norLAAM caused a significant decrease in the release of human chorionic gonadotropin. At this time, it is unclear whether a similar effect for norLAAM may occur in vivo and, if so, what the consequences would be on its role in implantation and normal fetal growth and development.

Received February 25, 2003; accepted April 1, 2003.

Address correspondence to: Dr. Mahmoud S. Ahmed, Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0587. E-mail: maahmed{at}utmb.edu






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