Drug interaction between mosapride and erythromycin without electrocardiographic changes

Area of Science:

• Pharmacology
• Clinical Pharmacology
• Drug Interactions

Background:

• Cisapride is known to cause QT prolongation and torsades de pointes, potentially via potassium channel blockade.
• Drug interactions with cytochrome P450 CYP3A4 inhibitors (e.g., macrolides, azoles) are a suspected mechanism for adverse cardiac events.

Purpose of the Study:

• To investigate the effects of mosapride on electrocardiogram (ECG) parameters and pharmacokinetics.
• To assess potential cardiac risks when mosapride is coadministered with erythromycin, a CYP3A4 inhibitor.

Main Methods:

• Ten healthy male volunteers received mosapride (15 mg/day) for 7 days.
• Mosapride was then coadministered with erythromycin (1200 mg/day) for 7 days.
• ECG parameters (QT interval, QTc) and mosapride plasma concentrations were monitored.

Main Results:

• Erythromycin increased mosapride Cmax by 1.6-fold and prolonged its half-life (t1/2) from 1.6 to 2.4 hours, indicating inhibited metabolism.
• No significant differences were observed in QT interval or QTc between mosapride alone and with erythromycin.
• No correlation was found between ECG parameters and plasma mosapride concentrations; QTc remained within normal limits.

Conclusions:

• Mosapride and erythromycin exhibit pharmacokinetic interaction due to CYP3A4 inhibition.
• Coadministration of mosapride and erythromycin did not significantly affect ECG parameters.
• The risk of severe clinical adverse events, such as QT prolongation and torsades de pointes, appears low with this drug combination.