Document Detail


Effect of pregnancy on nitrofurantoin disposition in mice.
MedLine Citation:
PMID:  19422048     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the effect of pregnancy on nitrofurantoin (NFT) disposition in wild-type and Bcrp1(-/-) mice. Pregnant and non-pregnant mice were administered NFT intravenously (5 mg/kg) or orally (10 mg/kg). Blood samples were collected at various times (5-60 min) after drug administration, plasma NFT concentrations determined by HPLC/UV, and pharmacokinetic parameters estimated. Dose-normalized area under the plasma concentration-time curve (AUC), terminal plasma half-life (T(1/2)), total plasma clearance (CL), and steady-state volume of distribution (V(ss)) of intravenous NFT in wild-type or Bcrp1(-/-) mice were not altered by pregnancy. After oral administration, pregnancy did not affect dose-normalized AUC of NFT in wild-type mice; however, dose-normalized AUC in Bcrp1(-/-) mice was decreased by approximately 70% by pregnancy. In conclusion, since Bcrp1 plays a minor role in the systemic clearance of NFT in female mice, pregnancy did not affect disposition of intravenous NFT despite the fact that Bcrp1 expression in the liver and kidney of mice is significantly induced by pregnancy. On the other hand, pregnancy may affect expression and activity of certain intestinal efflux transporters and/or metabolic enzymes in Bcrp1(-/-) mice, resulting in a drastic decrease in the systemic exposure of oral NFT in pregnant Bcrp1(-/-) mice.
Authors:
Yi Zhang; Lin Zhou; Jashvant D Unadkat; Qingcheng Mao
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  98     ISSN:  1520-6017     ISO Abbreviation:  J Pharm Sci     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-01     Completed Date:  2010-01-14     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4306-15     Citation Subset:  IM    
Copyright Information:
(c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association
Affiliation:
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington 98195-7610, USA.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics,  metabolism*
Animals
Anti-Infective Agents, Urinary / administration & dosage,  blood,  pharmacokinetics*
Area Under Curve
Chromatography, High Pressure Liquid
Dose-Response Relationship, Drug
Female
Half-Life
Injections, Intravenous
Metabolic Clearance Rate
Mice
Mice, Knockout
Nitrofurantoin / administration & dosage,  blood,  pharmacokinetics*
Pregnancy
Spectrophotometry, Ultraviolet
Tissue Distribution / drug effects
Grant Support
ID/Acronym/Agency:
HD044404/HD/NICHD NIH HHS; P50 HD044404-05/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/ATP-Binding Cassette Transporters; 0/Abcg2 protein, mouse; 0/Anti-Infective Agents, Urinary; 67-20-9/Nitrofurantoin
Comments/Corrections

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


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