Digoxin-quinidine interaction is well documented In the literature. The mechanism is, however, unknown. Previously, it was shown that quinidine reduced digoxin secretion by inhibiting P-glycoprotein (Pgp) in the renal tubule. Because Pgp is expressed in the small intestine to an extent no less than that in the kidney, the study was designed to investigate the possible effect of quinidine on the absorption and exsorption of digoxin in the rat Intestine. Results from the everted sac study using different Pgp inhibitors and Inducers support that digoxin is a substrate of Pgp in both jejunum and ileum. Plasma concentration of digoxin after intravenous administration Increased 2-fold when I mg/hr qulnidine was coinfused, whereas the amount that appeared in the intestinal lumen decreased by-40%. In the presence of quinidine, total clearance decreased from 318.0±19.3 to 167.1±11.0 mllhr, whereas intestinal clearance decreased from 28.8± 1.7 to I 1.1±1.6 mI/hr. In a separate study, H-labeIed digoxin was infused intravenously together with luminal perfusion of unlabeled digoxin in the intestine. The change of 3H-labeled digoxin concentrations In plasma and in the intestinal lumen was similar to those in the exsorptlon study. However, concentration of unlabeled digoxin In plasma or the intestinal lumen did not after significantly with the addition of quinidine. The absorption clearance In the control group (N= 6, 6.4±0.47 mI/hr) was significantly higher than that in the group with quinidine coadministration(N= 6, 4.8±0.31 mVhr p< 0.05). This indicates that quinidine may affect not only the elimination of digoxin, such as renal secretion, but also the absorpfion/exsorption of digoxin in the gastrointestinal tract. This study suggests that Pgp is involved in the drug interaction between digoxin and quinidine in the small intestine. ft is clinically important to understand the effect of quinldine on digoxin absorption for further assessment.

Digoxin, a drug used for the treatment of congestive heart failure, exhibits a narrow therapeutic index and is usually administered orally. Studies have indicated the interaction between digoxin and quinidine in clinical use (1, 2). However, the mechanism of quinidine-digoxin interaction is not fully elucidated. It has been reported that digoxin interacts with quinidine in different tissues (3, 4). Studies have dem-