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PMID: 16749853 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Methods to evaluate biliary excretion of drugs in humans: an updated review.

Molecular pharmaceutics ·Vol. 3 ·No. 3 ·2006-00-00 ·Pages 198-211

Ghibellini G, Leslie EM, Brouwer KL

Abstract

Determining the biliary clearance of drugs in humans is very challenging because bile is not readily accessible due to the anatomy of the hepatobiliary tract. The collection of bile usually is limited to postsurgical patients with underlying hepatobiliary disease. In healthy subjects, feces typically are used as a surrogate to quantify the amount of drug excreted via nonurinary pathways. Nevertheless, it is very important to characterize hepatobiliary elimination because this is a potential site of drug interactions that might result in significant alterations in systemic or hepatic exposure. In addition to the determination of in vivo biliary clearance values of drugs, the availability of in vitro models that can predict the extent of biliary excretion of drugs in humans may be a powerful tool in the preclinical stages of drug development. In this review, recent advances in the most commonly used in vivo methods to estimate biliary excretion of drugs in humans are outlined. Additionally, in vitro models that can be employed to investigate the molecular processes involved in biliary excretion are discussed to present an updated picture of the new tools and techniques that are available to study the complex processes involved in hepatic drug transport.

MeSH Terms
Bile/chemistry,metabolism Cells, Cultured Cholecystectomy Clinical Laboratory Techniques Cytoplasmic Vesicles Duodenum/chemistry Feces/chemistry Hepatocytes/chemistry Humans Intestinal Secretions/chemistry Pharmacokinetics
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ghibellini Giulia
School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Leslie Elaine M
Brouwer Kim L R
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Article Info
Journal
Molecular pharmaceutics
Abbr.
Mol Pharm
ISSN
1543-8384
DOI
10.1021/mp060011k
Published
2006-00-00
Pages
198-211
Language
English
Region
United States
NLM ID
101197791
PMCID
PMC2572858
Subset
IM
Grants
NCRR NIH HHS · M01 RR000046 · United States
NIGMS NIH HHS · R01 GM041935 · United States
NIGMS NIH HHS · R01 GM41935 · United States
NCRR NIH HHS · M01 RR000046-461417 · United States
NIGMS NIH HHS · R01 GM041935-16 · United States
NCRR NIH HHS · M01 RR000046-461156 · United States
NIGMS NIH HHS · R01 GM041935-15 · United States
NCRR NIH HHS · RR00046 · United States
External Links
PubMed source DOI: 10.1021/mp060011k PMC Full Text View journal details
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