Possible Interaction: Debrisoquin and Quinidine

“The extent to which quinidine altered these indices of encainide disposition was highly correlated with the metabolic ratio for debrisoquine oxidation (r = 0.62-0.95).”

“By pre-treatment with a typical CYP2D6 inhibitor, quinidine , the AUC0-8 value of 4-OH DB in High was decreased although such values in Low and uPA-/-/SCID mice did not change.”

“Although both quinidine and quinine are competitive inhibitors of debrisoquine 4-hydroxylase activity in rat and man, their potency is reversed.”

“ Quinidine is a potent inhibitor of debrisoquine 4-hydroxylase activity of human liver (IC50: 3.6 microM).”

“However, two of them were on quinidine , a well known inhibitor of debrisoquine oxidation.”

“In their study, they have also demonstrated that quinidine inhibits both CYP2D6- and CYP1A1-mediated debrisoquine 4-hydroxylation.”

“Both the S(+)-4- and 7-hydroxylations of debrisoquine were inhibited by quinidine in both populations.”

“A single oral dose (50 mg) of quinidine significantly increased the debrisoquine metabolic ratio in six healthy volunteers.”

“It is concluded that quinidine , but not its diastereoisomer quinine, is a potent selective inhibitor of the in vivo oxidation of debrisoquine and can produce an artifactual PM phenocopy in persons who are phenotypically extensive metaboliser (EM) phenotype status.”

“Biotransformation of substrates for the debrisoquine pathway can be markedly perturbed by even low doses of quinidine ; interindividual variability in drug interactions may have a genetic component.”

“ Quinidine was a potent inhibitor of the 4-hydroxylation of debrisoquine and the 1'-hydroxylation of bufuralol, with IC50 values of 0.7 and 0.2 microM, being around 100 times more potent in this respect than quinine.”