PHARMACOKINETICS OF THE GASTROKINETIC AGENT MOSAPRIDE CITRATE AFTER SINGLE AND MULTIPLE ORAL ADMINISTRATIONS IN HEALTHY-SUBJECTS

The pharmacokinetics and dose proportionality of mosapride citrate [4- (4-fluorobenzyl)-2-morpholinyl]methyl]benzamide citrate dihydrate, AS- 4370, CAS 112885-42-4) were investigated in healthy male volunteers. T he subjects were given a single oral dose (5, 10, 20 and 40 mg, each o f 5 subjects) and a multiple oral dose (20 mg t.i.d. for one day, and 10 and 20 mg t.i.d. for 8 days, each of 5 subjects). Food effects on t he pharmacokinetics of mosapride was also evaluated after a single ora l 10 mg dose by an open, two-way crossover method. Mean plasma levels of mosapride reached a peak 0.5-1 h after single dosing of 5, 10, 20 a nd 40 mg. The peaks were dose-related with values of 25.1 51.2, 157.8 and 280.6 ng/ml, respectively, and were followed by a first-order decr ease with apparent half-lives of 1.4-2.0 h. The C. and AUC increased i n proportion to the dose, indicating linear pharmacokinetics of mosapr ide up to 40 mg. The C(max) of M-1, a des-4-fluorobenzyl metabolite, w as 1/6 of that of the unchanged drug. Urinary excretion of the unchang ed mosapride and M-1 during 48 h after single dosing accounted for 0.1 -0.4% and 7.0-11.0% of the dose, respectively. There were no significa nt changes in the plasma concentration-time profiles and urinary excre tions between single and multiple doses, indicating that the pharmacok inetics of mosapride in man was not altered by its multiple administra tion. Plasma levels of mosapride reached steady state on day 2 of mult iple administration. Food intake scarcely affected the pharmacokinetic s of mosapride.