Document Detail


Transplacental transfer and distribution of pravastatin.
MedLine Citation:
PMID:  24070396     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The objective of the study was to determine the bidirectional transfer of pravastatin across the dually perfused term human placental lobule and its distribution between the tissue and maternal and fetal circuits.
STUDY DESIGN: The transfer of pravastatin was determined in the maternal-to-fetal (n = 11) and fetal-to-maternal (n = 10) directions. Pravastatin was coperfused with its [(3)H]-isotope and the marker compound antipyrine (20 μg/mL) and its [(14)C]-isotope. The concentration of pravastatin in the perfused tissue and the maternal and fetal circuits was determined using liquid scintillation spectrometry. Inside-out vesicles prepared from placental brush border membranes were utilized to investigate the role of efflux transporters in the transplacental transfer of pravastatin.
RESULTS: Pravastatin was transferred from the maternal to the fetal circuit and vice versa. In the maternal-to-fetal direction, the distribution of pravastatin at the end of experiment was as follows: 14 ± 5% of the drug was retained by the tissue, 68 ± 5% remained in the maternal circuit, and 18 ± 4% was transferred to the fetal circuit. The normalized transfer of pravastatin (clearance index) to antipyrine in the fetal-to-maternal direction (0.48 ± 0.07) was higher than its transfer in the maternal-to-fetal direction (0.36 ± 0.07, P < .01). Furthermore, pravastatin inhibited the adenosine triphosphate (ATP)-dependent uptake of the paclitaxel and estrone sulfate.
CONCLUSION: The transfer of pravastatin across the dually perfused placental lobule suggests that fetal exposure to pravastatin is plausible. The higher transfer of pravastatin in the fetal-to-maternal direction than the reverse as well as its inhibition of the ATP-dependent uptake of [(3)H]-paclitaxel and [(3)H]-estrone sulfate strongly suggest the involvement of efflux transporters in decreasing its transfer across the placenta and support pravastatin's favorable pharmacokinetic profile in pregnancy.
Authors:
Tatiana N Nanovskaya; Svetlana L Patrikeeva; Jonathan Paul; Maged M Costantine; Gary D V Hankins; Mahmoud S Ahmed
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  American journal of obstetrics and gynecology     Volume:  209     ISSN:  1097-6868     ISO Abbreviation:  Am. J. Obstet. Gynecol.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-27     Completed Date:  2013-12-11     Revised Date:  2014-01-15    
Medline Journal Info:
Nlm Unique ID:  0370476     Medline TA:  Am J Obstet Gynecol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  373.e1-5     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 Mosby, Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
Maternal-Fetal Exchange*
Placenta / metabolism*
Pravastatin / pharmacokinetics*
Pregnancy
Grant Support
ID/Acronym/Agency:
U10 HD047891/HD/NICHD NIH HHS; U10-HD 047891/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; KXO2KT9N0G/Pravastatin

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


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