Role of human placental efflux transporter P-glycoprotein in the transfer of buprenorphine, levo-alpha-acetylmethadol, and paclitaxel.
This study examines the role of placental P-glycoprotein (P-gp) in the transfer of buprenorphine (BUP) and L-alpha-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 (TR (f)), maternal clearance (Cl (m)), and clearance index (Cl (index)). 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%, Cl (m) 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.
Nekhayeva
Ilona A
IA
Department of Clinical Pharmacology, Belarussian State Medical University, Minsk, Republic of Belarus.
Nanovskaya
Tatiana N
TN
Hankins
Gary D V
GD
Ahmed
Mahmoud S
MS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D000166:Acridines / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism; D002047:Buprenorphine / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008692:Methadyl Acetate / Q000378:metabolism*; D017239:Paclitaxel / Q000378:metabolism*; D010920:Placenta / Q000502:physiology*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000166:Acridines; D000701:Analgesics, Opioid; D000972:Antineoplastic Agents, Phytogenic; D044005:Tetrahydroisoquinolines; D002047:Buprenorphine; D008692:Methadyl Acetate; C083501:Elacridar; D017239:Paclitaxel