No abstract

The rapid absorption of zolmitriptan nasal spray may explain the faster relief from migraine reported in patients compared with oral zolmitriptan.

The concentrations of telithromycin, a new ketolide antimicrobial agent, in alveolar macrophages (AMs) and bronchoalveolar epithelial lining fluid (ELF) were determined in order to investigate the transfer of the drug into target tissue, relative to plasma, following multiple oral doses of telithromycin. Twenty-four healthy male Japanese volunteers were randomly allocated to four groups. Each subject was given 600 or 800 mg of telithromycin once daily for 5 days, followed by bronchoalveolar lavage (

Pharmacokinetic parameters of zolmitriptan were similar between Caucasian and Japanese volunteers.

SUMMARYQT 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 C max 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. (Jpn Heart J 2003; 44: 225-234) Key words: Mosapride, Erythromycin, Drug interaction IN recent years, cardiovascular adverse effects including QT prolongation and torsades de pointes have been documented 1,2) in patients administered cisapride, a gastroprokinetic drug with serotonin 5-HT 4 receptor agonistic activity. Its blocking action on delayed rectifier potassium channels in myocytes has been suggested as the mechanism.3,4) Cisapride, which is metabolized by cytochrome P450 CYP3A4 species, undergoes inhibition of its biotransformation by CYP3A4 From