Possible Interaction: Ketoconazole and Quinidine

“ Ketoconazole , which is a potent inhibitor of CYP3A4/5, had a strong inhibitory effect on their formation, and the M4 formation from R(+)-cibenzoline was inhibited by quinidine by 45%.”

“In pooled human liver microsomes, formation of both metabolites was partially inhibited by both quinidine and ketoconazole , suggesting that CYP2D6 and CYP3A enzymes are involved in the metabolism of CJ-12,458.”

“In human liver microsomes, the mean K(m) (+/-S.E. ) was 14.4 +/- 2.0 microM. A screen of the chemical inhibitors omeprazole (10 microM), quinidine (10 microM), sulfaphenazole (10 microM), and ketoconazole (2.5 microM) only revealed detectable inhibition with ketoconazole.”

“ Quinidine almost completely inhibited the CYP2D6-mediated de-esterification at the concentration of 1 x 10(-6) M. Ketoconazole and troleandomycin inhibited the CYP3A4-mediated reaction in a dose-related manner.”

“ Ketoconazole had the most pronounced inhibitory effect on the biotransformation of both substrates, while for quinidine and furafylline there was only a weak or no influence.”

“Formation of all three products was reduced to approximately 20% of control values by 1 μM ketoconazole; quinidine at 1 μM produced a small reduction in formation (91–94% of control) of two of the metabolites.”

“ Ketoconazole , an inhibitor of CYP3A4, inhibited competitively CPHP formation (Ki=0.1 microM), whereas sulphaphenazole (CYP2C9), furafylline (CYP1A2) and quinidine (CYP2D6) gave only little inhibition (IC50 > 100 microM).”

“Dual inhibitors of both P-gp and Cyp3a (verapamil and ketoconazole ) increased the concentration of Qi in the jejunum and ileum, but less 3-hydroxy-quinidine was produced due to inhibition of Cyp3a.”

“The analysis of the obtained pharmacokinetic parameters showed that, KTZ significantly reduced total body clearance of QUN by 35%, while CIM did not.”

“Co-administration of KTZ increased C(max) of QN to about 1.5-fold.”