Hepatic clearance parameters affecting

After 16 healthy subjects took both diltiazem 60 mg and moracizine 250 mg every 8 hours for 7 days, the maximum plasma concentration of moracizine was increased by 89%, the AUC was increased by 121%, and clearance was decreased by 54%. In contrast, the maximum plasma concentration and AUC of diltiazem decreased by 36% and clearance was increased by 52%. The AUCs for the diltiazem metabolites were not sig-nifrcantly affected. No clinically signifrcant changes in ECU parameters were seen. However, the frequency of adverse events (e.g. headache, dizziness, paraesthesia) was greater on concurrent use (76%) than with either drug alone (54 and 45% for moracizine and diltiazem respectively). Diltiazem probably inhibits the hepatic metabolism of moracizine while moracizine increases that of diltiazem. The clinical signifrcance of this interaction is not known. However, particular caution is advised if diltiazem and moracizine are given concurrently, in light of the increase in adverse events. Dose adjustments may also be required to obtain optimum therapeutic responses. 

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