Possible Interaction: Digoxin and Quinine

“ Digoxin uptake into the slice showed a temperature-dependent component and was stereoselectively inhibited by quinine , which is compatible with the involvement of a carrier-mediated uptake mechanism.”

“Quinidine, quinine and verapamil but not probenecid or spironolactone were found to inhibit the biliary secretion of unchanged digoxin.”

“In a previous study in rat hepatocytes, marked inhibition of digoxin uptake by quinine and only minimal inhibition by the diastereomer quinidine was demonstrated, showing clear stereoselectivity in transport inhibition.”

“A marked reduction was found in … steady‐state biliary clearance of digoxin from control value 134 ± 57 ml/min (mean ± …) to 87 ± 39 ml/min during treatment with quinine (p < 0.05) and from 95 ± 24 to 55 ± 27 …/min during treatment with quinidine (p < 0.01; n = 4).”

“These findings explain the difference in magnitude between quinidine and quinine in regard to the interaction with digoxin and imply a different degree of stereoselectivity for these isomers in the renal and biliary secretory systems of digoxin.”

“An increase in quinine dose (to 750 mg/day) caused further increments in plasma digoxin levels, whereas renal digoxin clearance remained unchanged.”

“ Quinine (250 mg/day) increased mean plasma digoxin concentration from 0.64 +/- 0.12 to 0.80 +/- 0.18 ng/ml (p less than 0.05) within one week.”

“ Quinine elevates plasma digoxin concentrations in a stepwise fashion probably due to an impairment of extrarenal digoxin clearance.”

“ Quinine reduced digoxin total body clearance by 26% from 2.98 to 2.22 ml/min/kg (p < 0.03).”

“These results suggest that quinine alters digoxin metabolism or biliary secretion, reducing digoxin total body clearance by a mechanism that is qualitatively similar, but quantitatively different, from quinidine.”

“Concentrations of the drugs in perfusion medium and bile were followed up to 2 h. RESULTS A marked reduction in the initial medium disappearance rate of digoxin and ouabain by quinine was found, whereas quinidine did not affect the hepatic disposition of the cardiac glycosides.”

“The stereoselective inhibition of digoxin and ouabain clearance by quinine , and not by quinidine, was shown to be due to an effect on the hepatic uptake level rather than on the metabolic conversion and/or the biliary excretion steps.”

“Indogs, a single dose of quinine led to a redistribution of digoxin in tissues, which was reflected by an acute and biphasic change in plasma and blood concentrations.”