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Pharmaceutics 2010, 2(1), 61-77; doi:10.3390/pharmaceutics2010061
Article

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

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Received: 1 February 2010; in revised form: 5 March 2010 / Accepted: 11 March 2010 / Published: 15 March 2010
(This article belongs to the Special Issue What's on Board in Pharmaceutics)
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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.
Keywords: ATP-binding cassette; ABCB1; P-glycoprotein; pregnane X receptor; pregnenolone 16α-carbonitrile; induction; digoxin; pharmacokinetics; disposition; intestinal transport ATP-binding cassette; ABCB1; P-glycoprotein; pregnane X receptor; pregnenolone 16α-carbonitrile; induction; digoxin; pharmacokinetics; disposition; intestinal transport
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Lowes, S.; Haslam, I.S.; Fihn, B.-M.; Hilgendorf, C.; Karlsson, J.E.; Simmons, N.L.; Ungell, A.-L. The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat. Pharmaceutics 2010, 2, 61-77.

AMA Style

Lowes S, Haslam IS, Fihn B-M, Hilgendorf C, Karlsson JE, Simmons NL, Ungell A-L. The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat. Pharmaceutics. 2010; 2(1):61-77.

Chicago/Turabian Style

Lowes, Simon; Haslam, Iain S.; Fihn, Britt-Marie; Hilgendorf, Constanze; Karlsson, Johan E.; Simmons, Nicholas L.; Ungell, Anna-Lena. 2010. "The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat." Pharmaceutics 2, no. 1: 61-77.



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