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Am J Perinatol 2006; 23(7): 423-430
DOI: 10.1055/s-2006-951301
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

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
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Publication History

Publication Date:
25 September 2006 (online)

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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 (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: TRf, 123 ± 20%, Clm 116 ± 23%, and Clindex 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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Mahmoud S AhmedPh.D. 

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

301 University Blvd., Galveston, TX 77555-0587