건강한 한국인 자원자에서 테가세로드(Tegaserod) 반복 투여에 의한 안전성 및 약동학 평가

Evaluation of Safety and Pharmacokinetics of Tegaserod After Multiple Oral Administrations in Healthy Korean Subjects

Background: Tegaserod is a selective partial agonist at the $5HT_4$ receptor. Tegaserod belongs to a new class of agents in development for the treatment of functional motility disorders of the gastrointestinal(GD tract. This Phase I clinical study was conducted to evaluate the safety and pharmacokinetics(PK) of tegaserod in Korean for bridging foreign clinical data. Methods: A randomized, double blind, placebo controlled, multiple oral dosing(2 mg, 6 mg, twice a day for 7 days) study was conducted in 32 healthy Korean volunteers(M:F=16:16). Serial blood samples for pharmacokinetic analysis were taken. Safety evaluation was performed by adverse event monitoring, physical examination including vital signs, ECG and clinical labororatory analysis. Results: Plasma concentration of tegaserod reached peak levels $1.0{\sim}1.5$ hours after single and multiple dose administration and declined with a terminal half life of about 12 hours. PK parameters of 2 mg group were not calculated well due to low plasma concentration. Tegaserod showed linear pharmacokinetic characteristics, and little accumulation occurred after multiple administrations. There were no gender differences in PK parameters. Neither serious nor dose-limiting adverse events were observed. PK of tegaserod in Koreans was comparable to Caucasian data. Conclusion: Tegaserod was found to be safe and showed similar PK characteristics to Caucasians. This study demonstrates comparability between Korean and Caucasian healthy subjects in the PK of tegaserod and supports the use of Caucasian data in the evaluation of PK, safety, and efficacy for Korean patients.