This study examines the role of placental P-glycoprotein (P-gp) in the transfer of buprenorphine (BUP) and L-α-acetylmethadol (LAAM) across the dually perfused human placental lobule. BUP (10 ng/mL) and LAAM (35 ng/mL) were perfused in the maternal-to-fetal direction. The following kinetic parameters were determined: fetal transfer rate (TRf), maternal clearance (Clm), and clearance index (Clindex). The opiates were perfused in the presence of P-gp inhibitor GF120918 (experimental group) and in its absence (control group). The kinetic parameters for the control group were set at 100% and were as follows for LAAM in the experimental group: TR f, 123 ± 20%, Clm 116 ± 23%, and Cl index 123 ± 22% (P < 0.05). The corresponding parameters for BUP were not different from controls. The data indicate that LAAM, but not BUP, is extruded by the efflux transporter P-gp. Therefore, it is reasonable to assume that the activity of P-gp could be one of the factors affecting the extent of fetal exposure to LAAM during pregnancy.
- Human placenta
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Obstetrics and Gynecology