Received for publication February 27, 2003.
Revised March 18, 2003.
Accepted for publication April 1, 2003.

Transfer of L--acetylemthadol (LAAM) and L--acetyl-N-normethadol (norLAAM) by the Perfused Human Placental Lobule

Abstract

The opiates buprenorphine (BUP) and L--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. Since LAAM is rapidly metabolized to the pharmacologically active L--acetyl-N-normethadol (norLAAM) it was included in this investigation. The two opiates were transfused at a concentration of 35 ng/ml that has been reported for their plasma levels in patients under treatment. The drugs exhibited similar pharmacokinetic profiles characterized by an initial fast phase of distribution into placental tissue followed by their low transfer to the fetal circuit. During the 4-hour 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 hCG. At this time, it is unclear if a similar effect for norLAAM may occur in vivo and if so, what would the consequences be on its role in implantation and normal fetal growth and development.

Key words: LAAM, human, norLAAM, placenta, pregnancy, transfer