Pharmacokinetics of oral and intravenous administration of digoxin after intestinal ischemia-reperfusion

Abstract

Intestinal ischemia-reperfusion (I/R) causes gut dysfunction characterized by decreased basement membrane integrity and decreased barrier function. Indeed, it has been reported that the absorption of several drugs is altered after intestinal I/R. Intestinal I/R also promotes multi-organ failure (MOF). The liver and kidney can be affected by MOF after intestinal I/R. However, little is known about the alteration of pharmacokinetics after intravenous administration in intestinal I/R injury. In the present study, we investigated pharmacokinetics of digoxin after oral administration and intravenous administration in intestinal I/R injury. Plasma digoxin concen-tration in I/R rats after oral administration was not significantly altered at any time compared with that in sham-operated rats. Plasma digoxin concentration in rats reperfused for 1h after intravenous administration was significantly higher than that in sham-operated rats. Plasma digoxin concentrations in rats reperfused for 6 and 24h were the same as those in sham-operated rats. The area under the concentration-time curve after intravenous administraion (AUCi.v.) and total clearance (CLtot) in rats reperfused for 1h was 1.89- and 0.57-fold higher than that in sham-operated rats. However, elimination rate (ke) and half-life (t1/2) in rats reperfused for 1h were not altered. Distribution volume (Vd) in rats reperfused for 1h was decreased than that in sham-operated rats, but there was not statistical difference. These results suggest that intestinal I/R affected the Vd of digoxin, and plasma concentration of digoxin was increased. The present study suggests that understanding pharmacokinetics of drug after intravenous administration in intestinal I/R injury is important to provide valuable information for safe drug therapy for intestinal I/R patients. © 2010 Pharmaceutical Society of Japan.