Document Detail


Influence of P-glycoprotein on the transplacental passage of cyclosporine.
MedLine Citation:
PMID:  11745716     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The transfer kinetics of cyclosporine across the dually perfused rat placenta in the maternal to fetal direction and a possible involvement of P-glycoprotein were investigated. The transplacental clearance of cyclosporine in the materno-fetal direction was found to be dependent on the maternal inflow concentration of cyclosporine. Coadministration of cyclosporine with an excess of quinidine or chlorpromazine into the maternal compartment revealed 1.7- and 1.9-fold increase in cyclosporine concentration in the fetal compartment. In the experiments where quinidine was present both in the maternal and fetal compartments, cyclosporine appeared in the fetal compartment significantly faster, and its amount was three times higher when compared with controls. Conversely, quinidine or chlorpromazine did not affect the transplacental passage of L-[(3)H]-glucose. The interference of quinidine with the metabolism of cyclosporine in the placenta was excluded because only traces of M-1 and M-17 metabolites were found in the fetal solutions. Sodium azide, a mitochondrial respiratory inhibitor, was found to double the rate of cyclosporine, but not L-[(3)H]-glucose, passage across the placenta. Our findings indicate that P-glycoprotein pumps cyclosporine out of the trophoblast cells of the rat placenta in the ATP-dependent manner and restricts the passage of cyclosporine across the placental barrier.
Authors:
P Pávek; Z Fendrich; F Staud; J Malákova; H Brozmanová; M Láznícek; V Semecký; M Grundmann; V Palicka
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  90     ISSN:  0022-3549     ISO Abbreviation:  J Pharm Sci     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-12-17     Completed Date:  2002-03-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1583-92     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1583-1592, 2001
Affiliation:
Department of Pharmacology and Toxicology, Faculty of Pharmacy Hradec Králové, Charles University Prague, Czech Republic.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chlorpromazine / pharmacology
Cyclosporins / pharmacokinetics*
Female
Glucose / pharmacokinetics
Kinetics
Maternal-Fetal Exchange*
P-Glycoprotein / physiology*
Perfusion
Placenta / metabolism*
Pregnancy
Quinidine / pharmacology
Rats
Rats, Wistar
Sodium Azide / pharmacology
Time Factors
Chemical
Reg. No./Substance:
0/Cyclosporins; 0/P-Glycoprotein; 26628-22-8/Sodium Azide; 50-53-3/Chlorpromazine; 50-99-7/Glucose; 56-54-2/Quinidine

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