Pharmacokinetics of the gastrokinetic agent mosapride citrate after single and multiple oral administrations in healthy subjects
Sakashita, M.; Yamaguchi, T.; Miyazaki, H.; Sekine, Y.; Nomiyama, T.; Tanaka, S.; Miwa, T.; Harasawa, S.
Arzneimittel-Forschung 43(8): 867-872
1993
ISSN/ISBN: 0004-4172 PMID: 8216445 Document Number: 1120
The pharmacokinetics and dose proportionality of mosapride citrate ((+-)-4-amino-5-chloro-2-ethoxy-N-((4-(4-fluorobenzyl)-2-morpholinyl)methyl)benzamide citrate dihydrate, AS-4370, CAS 112885-42-4) were investigated in healthy male volunteers. The subjects were given a single oral dose (5, 10, 20 and 40 mg, each of 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 effect on the pharmacokinetics of mosapride was also evaluated after a single oral 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 and 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 decrease with apparent half-lives of 1.4-2.0 h. The C-max and AUC increased in proportion in the dose, indicating linear pharmacokinetics of mosapride up to 40 mg. The C-max of M-1, a des-4-fluorobenzyl metabolite, was 1/6 of that of the unchanged drug. Urinary excretion of the unchanged 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 significant changes in the plasma concentration-time profiles and urinary excretions between single and multiple doses, indicating that the pharmacokinetics of mosapride in man was not altered by its multiple administration. Plasma levels of mosapride reached steady state on day 2 of multiple administration. Food intake scarcely affected the pharmacokinetics of mosapride.
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