Drug Interaction Between Mosapride and Erythromycin Without Electrocardiographic Changes
| Autor: | Masao Tateno, Koichi Nagasawa, Hirokazu Saitoh, Isao Dendo, Takao Katoh, Tsuyoshi Nakamura, Shinichi Kobayashi, Norihiko Ohno |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Adult
Male Morpholines Cmax Erythromycin Torsades de pointes Pharmacology QT interval Electrocardiography Pharmacokinetics medicine Humans Drug Interactions business.industry Drug interaction medicine.disease Mosapride Anti-Bacterial Agents Cisapride Benzamides Electrocardiography Ambulatory Dopamine Antagonists Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Japanese Heart Journal. 44:225-234 |
| ISSN: | 1348-673X 0021-4868 |
| DOI: | 10.1536/jhj.44.225 |
| Popis: | QT prolongation and torsades de pointes have been documented in patients administered cisapride and its blocking of potassium channels in myocytes has been suggested as the mechanism. An interaction with cytochrome P450 CYP3A4 inhibitor drugs like macrolide and azole antifungals is also thought to be a possible mechanism. Since mosapride has characteristics similar to cisapride, we examined the effects of mosapride on the electrocardiogram and pharmacokinetics before and after its coadministration with erythromycin. Ten healthy male volunteers were repeatedly administered mosapride 15 mg/day for 7 days followed by coadministration with erythromycin 1200 mg/day for 7 days. Coadministration with erythromycin resulted in a 1.6-fold increase in the Cmax of mosapride and prolongation of t(1/2) from 1.6 to 2.4 hours, indicating the inhibition of mosapride metabolism. However, there were no significant differences in the QT interval and QTc between mosapride alone and concomitant use with erythromycin. There was no correlation between the electrocardiographic parameters and plasma mosapride concentrations, and no case exceeded the upper limit of the normal range of QTc. Although there was a certain pharmacokinetic interaction between mosapride and erythromycin, their coadministration did not affect the electrocardiogram at all, indicating a reduced likelihood of severe clinical adverse events like QT prolongation and torsades de pointes. |
| Databáze: | OpenAIRE |
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