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The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat

Lowes, Simon, Haslam, Iain S., Fihn, Britt-Marie, Hilgendorf, Constanze, Karlsson, Johan E., Simmons, Nicholas L. and Ungell, Anna-Lena (2010) The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat. Pharmaceutics, 2 (1). pp. 61-77. ISSN 1999-4923

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Abstract

The effect of Pgp induction in rats by pregnenolone 16α-carbonitrile (PCN) (3 days, 35 mg/kg/d, p.o.) on digoxin pharmacokinetics and intestinal transport has been assessed. After intravenous or oral digoxin dosing the arterial and hepatic portal vein (oral) AUC(0-24h) were significantly reduced by PCN pre-treatment. Biliary digoxin clearance increased 2-fold following PCN treatment. PCN significantly increased net digoxin secretion (2.05- and 4.5-fold respectively) in ileum and colon but not in duodenum or jejunum. This increased secretion correlated with increased Pgp protein expression in ileum and colon. Both intestinal and biliary excretion therefore contribute to altered digoxin disposition following PCN.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > RM Therapeutics. Pharmacology
Schools: School of Applied Sciences
School of Applied Sciences > Biomolecular Sciences Research Centre
Depositing User: Iain Haslam
Date Deposited: 10 Nov 2015 16:54
Last Modified: 01 Dec 2016 00:53
URI: http://eprints.hud.ac.uk/id/eprint/26446

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