The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat
نویسندگان
چکیده
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.
منابع مشابه
P-glycoprotein and an unstirred water layer barring digoxin absorption in the vascularly perfused rat small intestine preparation: induction studies with pregnenolone-16alpha-carbonitrile.
Digoxin, a substrate of P-glycoprotein (Pgp) and cytochrome P450 3a (Cyp3a), was used to illustrate the inductive effects of pregnenolone-16alpha-carbonitrile (PCN), a ligand of the pregnane X receptor, on the absorption and disposition of [3H]digoxin in the vascularly perfused rat small intestine preparation. Although increased Cyp3a protein was observed with Western blotting analysis after PC...
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