Role of Human Placental Efflux Transporter P-Glycoprotein in the Transfer of Buprenorphine, Levo-α-Acetylmethadol, and Paclitaxel

Ilona A. Nekhayeva; Tatiana N. Nanovskaya; Gary D. V. Hankins; Mahmoud S. Ahmed

doi:10.1055/s-2006-951301

American Journal of Perinatology, Inhaltsverzeichnis

Am J Perinatol 2006; 23(7): 423-430
DOI: 10.1055/s-2006-951301

Role of Human Placental Efflux Transporter P-Glycoprotein in the Transfer of Buprenorphine, Levo-α-Acetylmethadol, and Paclitaxel

Ilona A. Nekhayeva¹ , Tatiana N. Nanovskaya² , Gary D.V Hankins² , Mahmoud S. Ahmed² ^, ³

¹Department of Clinical Pharmacology, Belarussian State Medical University, Minsk, Republic of Belarus
²Department of Obstetrics & Gynecology, University of Texas Medical Branch, Galveston, Texas
³Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, Texas

Abstract

ABSTRACT

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 (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.

KEYWORDS

Buprenorphine - levo-α-acetylmethadol - P-glycoprotein - human placenta

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Referenzen

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Mahmoud S AhmedPh.D.

Professor, Departments of Obstetrics & Gynecology and Pharmacology & Toxicology, University of Texas Medical Branch

301 University Blvd., Galveston, TX 77555-0587