Document Detail


Role of P-glycoprotein in transplacental transfer of methadone.
MedLine Citation:
PMID:  15876424     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Methadone is the therapeutic agent of choice for treatment of the pregnant opiate addict. However, little is known on the factors affecting its concentration in the fetal circulation during pregnancy and how it might relate to neonatal outcome. Therefore, a better understanding of the function of placental metabolic enzymes and transporters should add to the knowledge of the role of the tissue in the disposition of methadone and its relation to neonatal outcome. We hypothesized that the expression and activity of the placental efflux transporter P-glycoprotein (P-gp) would affect the transfer of methadone to the fetal circulation. Data obtained utilizing dual perfusion of placental lobule and monolayers of Be-Wo cell line indicated that methadone is extruded by P-gp. Transfer of methadone to the fetal circuit was increased by 30% in the presence of the P-gp inhibitor GF120918 while the transfer of paclitaxel, a typical substrate of the glycoprotein, was increased by 50%. In the Be-Wo cell line, methadone and paclitaxel uptake was also increased in the presence of the P-gp inhibitor cyclosporin A. Moreover, the expression of P-gp in placental brush-border membranes varied between term placentas. Taken together, these data strongly suggest that the concentration of methadone in the fetal circulation is affected by the expression and activity of P-gp. It is reasonable to speculate that placental disposition of methadone affects its concentration in the fetal circulation. If true, this may also be directly related to the incidence and intensity of neonatal abstinence syndrome (NAS).
Authors:
Tatiana Nanovskaya; Ilona Nekhayeva; Nedra Karunaratne; Kenneth Audus; Gary D V Hankins; Mahmoud S Ahmed
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  69     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-06     Completed Date:  2005-07-19     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1869-78     Citation Subset:  IM    
Affiliation:
Department of Obstetrics & Gynecology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0587, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Dose-Response Relationship, Drug
Female
Humans
Maternal-Fetal Exchange / drug effects*,  physiology*
Methadone / pharmacokinetics*
P-Glycoprotein / physiology*
Pregnancy
Protein Binding / drug effects,  physiology
Grant Support
ID/Acronym/Agency:
DA-13431-05/DA/NIDA NIH HHS; HD39878-03/HD/NICHD NIH HHS; P01 HD039878-01A10002/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/P-Glycoprotein; 76-99-3/Methadone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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