Pharmacokinetics and Safety of Indisetron Tablets in Healthy Subjects-Multiple-oral Dose Study-
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Accession number;05A0015061
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| Title;Pharmacokinetics and Safety of Indisetron Tablets in Healthy Subjects-Multiple-oral Dose Study- |
| Author;
YAMADA TADASHI
(Nisshin Flour Milling Co., Ltd.)
TADOKORO TOYOHIRO
(Nisshin Flour Milling Co., Ltd.)
NAKATA FUMIHISA
(Nisshin Flour Milling Co., Ltd.)
YONEZAWA KATSUNOBU
(Nisshin Flour Milling Co., Ltd.)
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Journal Title;Japanese Pharmacology & Therapeutics
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Journal Code:Z0947A
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ISSN:0386-3603
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VOL.32;NO.11;PAGE.815-821(2004)
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| Figure&Table&Reference;FIG.3, TBL.5, REF.3 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Objectives: Indisetron is a 5-hydroxytryptamine 3 receptor antagonist and an anti-emetic agent. It shows also 5-hydroxytryptamine 4 antagonistic activity in pharmacological profiles. A multiple-oral dose study as phase I trial for healthy male volunteers was performed to show the tolerability and the pharmacokinetic profiles at a dose of 16mg twice a day for 7 consecutive days (once a day on Day 1 and Day 7). Methods: Subjects were assigned randomly to Indisetron group and placebo group, and the trial was performed under single blind. They were administrated the Indisetron tablets orally at 30 minutes before morning and evening meals. As for pharmacokinetics, the plasma and urinary concentrations of indisetron and its metabolites were measured, and then pharmacokinetic parameters were evaluated. The safety was estimated by laboratory test, vital signs, signs and symptoms. Results: 9 healthy male adult volunteers were enrolled and 6 subjects were administrated indisetron in this study. As for adverse drug reactions, 2 subjects were presented with constipation and increase in serum amylase respectively, and not significant problems clinically. The plasma concentrations of indisetron were suggested to be achieved in steady state by Day 3. No changes of the pharmacokinetics and accumulation of indisetron by the repeated administration were indicated. And it was revealed that plasma protein binding, urinary excretion, renal clearance of the unchanged drug, the plasma concentration, urinary excretion ratio of the metabolites were not affected by the repeated administration. Conclusions: It showed no clinical problem of pharmacokinetic profiles in administration of 16mg multiple-oral dose of indisetron tablets in pre-prandial. (author abst.) |
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