RT Journal Article
SR Electronic
T1 Transfer of <span class="sc">l</span>-α-Acetylmethadol (LAAM) and  <span class="sc">l</span>-α-Acetyl-<em>N</em>-normethadol (norLAAM) by the Perfused  Human Placental Lobule
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 205
OP 212
DO 10.1124/jpet.103.050690
VO 306
IS 1
A1 Nanovskaya, Tatiana N.
A1 Deshmukh, Sujal V.
A1 Miles, Rachel
A1 Burmaster, Steve
A1 Ahmed, Mahmoud S.
YR 2003
UL http://jpet.aspetjournals.org/content/306/1/205.abstract
AB The agonists buprenorphine and l-α-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. The American Society for Pharmacology and Experimental Therapeutics