연구소 소식

미국임상약리학회 2010년 정기 학술대회(ASCPT 2010)에서 약리학교실에서 박사학위를 받고 박사후연구원으로 근무하고 있는 Pan Wei 연구원이 제출한 초록이 Presidential Trainee Award 로 선정되었으며, 해당 내용에 대하여 구연발표자로 초청되었습니다.

미국임상약리학회에서는 매년 정례회의에서 수련중인 임상약리연구자들이 제출한 초록중에서 뛰어난 연구내용에 대하여 선정하고 있습니다. 역대 Presidential Trainee Award 수상자는 세계적으로 연구성과가 뛰어난 대학이나 연구실의 신진 연구자에게 수여되었기 때문에 이번 Pan Wei 연구원의 수상과 구연초청은 교실에서 수행중인 연구내용이 세계적으로 주목받고 있음을 확인할수 있었습니다.

관련학회정보와 초록내용은 다음과 같습니다.

[학회정보]
행사명: ASCPT 2010 Annual Meeting
기간: 2010.03.17-03.20
장소: Atlanta Marriott Marquis, Atlanta, GA

[Abstract]
<U>Effects of clopidogrel and clarithromycin on the disposition of sibutramine and its active metabolites M1 and M2 in vivo in relation to CYP2B6 genetic polymorphism.</U>

Wei Pan, Soo Kyung Bae, Eon-Jeong Shim, Seong Eun Park, Ji Hong Shon, Jae Gook Shin

It has been demonstrated that CYP2B6 is a major catalyst in in vitro metabolism of sibutramine into its active metabolites M1 and M2 with the modest contribution of CYP2C19 and CYP3A4/5. This study was to evaluate the effect of clopidogrel as CYP2B6 inhibitor and clarithromycin as CYP3A4/5 inhibitor on the disposition of sibutramine and its metabolites in relation to CYP2B6 genotype.
In a 3-phase randomized cross-over design with 2-week washouts, 20 healthy Korean subjects (CYP2B6*1/*1=7; *1/*6=7; *6/*6=6) received a single 15mg oral dose of sibutramine on the 4th day of clopidogrel (75 mg/day), clarithromycin (250 mg twice daily) or neither. Sibutramine and its metabolites in plasma were analyzed using LC/MS/MS.

The genotype of CYP2B6 significantly affected the disposition of sibutramine and its metabolites. Both clopidogrel and clarithromycin significantly increased the concentration of sibutramine and decreased the metabolic conversion of sibutramine into the metabolites. The CYP2B6*6/*6 group when pretreated with clarithromycin showed the highest exposure of sibutramine and the lowest metabolic conversion ratio into its metabolites.
The co-administration of clopidogrel and clarithromycin greatly altered the disposition of sibutramine and its metabolites. The effect of CYP2B6 genotype on the disposition of sibutramine could be augmented in the presence of clarithrymycin and clopidogrel pretreatment.