Sulphonylurea physiochemical-pharmacokinetic relationships in the pancreas and liver

Fanning, Kent J., Anissimov, Yuri G. and Roberts, Michael S. (2009) Sulphonylurea physiochemical-pharmacokinetic relationships in the pancreas and liver. Journal of Pharmaceutical Sciences, 98 8: 2807-2821. doi:10.1002/jps.21631

Author Fanning, Kent J.
Anissimov, Yuri G.
Roberts, Michael S.
Title Sulphonylurea physiochemical-pharmacokinetic relationships in the pancreas and liver
Journal name Journal of Pharmaceutical Sciences   Check publisher's open access policy
ISSN 0022-3549
Publication date 2009-08
Sub-type Article (original research)
DOI 10.1002/jps.21631
Volume 98
Issue 8
Start page 2807
End page 2821
Total pages 15
Editor Ronald T. Borchardt
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2010
Language eng
Subject 920105 Digestive System Disorders
920106 Endocrine Organs and Diseases (excl. Diabetes)
1115 Pharmacology and Pharmaceutical Sciences
Formatted abstract
This study examined the physicochemical-pharmacokinetic relationships for the sulphonylureas in the perfused rat pancreas and liver. Multiple indicator dilution studies were conducted with bolus injections of tolbutamide, chlorpropamide, gliclazide, glipizide, glibenclamide and glimepiride, and a reference marker albumin, in the perfused pancreas and liver. Individual solute pharmacokinetics were analysed using nonparametric moment analysis and nonlinear regression assuming a physiologically based pharmacokinetic model. All solutes had similar shaped outflow concentration-time profiles in both the pancreas and liver, but varied in extraction. Negligible drug extraction was evident in the pancreas. Hepatic extraction ranged from 0.03 (tolbutamide) to 0.52 (glibenclamide) and could be related to solute lipophilicity and perfusate protein binding. The sulphonylurea mean transit times in both the pancreas and liver varied four- and ninefold respectively and were related to the lipophilicity and perfusate protein binding of the drug. The permeability surface area product of sulphonylureas from the perfusate into the organs were greater in the liver and were mainly determined by lipophilicity (pancreas, r2 = 0.89; liver, r2 = 0.80). The distribution of the sulphonylureas in both the perfused pancreas and perfused liver was dependent on their lipophilicity and perfusate protein binding. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2807-2821, 2009
Keyword Log P
Passive diffusion/ transport
Structure- transport relationship
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 26 MAY 2009

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 29 Mar 2010, 15:53:25 EST by Fiona Mactaggart on behalf of Medicine - Princess Alexandra Hospital