지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
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Purpose: Telmisartan, an angiotensin receptor blocker has been known to be a potent blocker of both CYP2J2 and Pglycoprotein(P-gp) in vitro. This study aims to investigate the drug-drug interactions between telmisartan and ebastine,a CYP2J2 and P-gp substrate in rats. Method: Ebastine (10 mg/kg) was orally given in the presence and absence oftelmisartan (4 mg/kg, p.o.). Heparinized blood was serially taken and the plasma concentrations of ebastine and its threemetabolites (hydroxyebastine, carebastine and desalkylebastine) were determined using LC-MS/MS, and their pharmacokineticparameters were compared. Results: Peak concentrations (Cmax) and AUC of ebastine were significantly (p<0.05)increased in the presence of telmisartan by 2.1 and 1.9 times, respectively. While Cmax of hydroxyebastine was significantlyincreased by 1.9 times, the half-life of hydroxyebasteine was decreased significantly with telmisartan (p<0.05). There was no change in the pharmacokinetic parameters of carebastine, the active metabolite of ebastine, and desalkylebastinewas not detected in plasma. The systemic exposure of ebastine was significantly augmented by telmisartan, indicatingthat telmisartan may enhance the absorption of ebastine by blocking P-gp. Conclusion: Although telmisartanmay also partially contribute to inhibit the biotransformation to hydroxyebastine, the inhibitory action seemed to beoverridden by the enhancement of absorption, because the generation of hydroxyebastine was not diminished. In spiteof such interactions between telmisartan and ebastine, no clinical consequence could be expected due to no significantchange of the active metabolite, carebastine.
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참고문헌 (21)
참고문헌 신청
Cummins CL / 2002 / Unmasking the Dynamic Interplay between Intestinal P-Glycoprotein and CYP3A4 / J Pharmacol Exp Ther 300 : 1036 ~ 1045
Fenner KS / 2009 / Drug-drug interactions mediated through P-glycoprotein : clinical relevance and in vitroin vivo correlation using digoxin as a probe drug / Clin Pharmacol
Fujii T / 1997 / Studies on the firstpass metabolism of ebastine in rats / Arzneimittelforschung 47 : 949 ~ 953
Glavinas H / 2004 / The Role of ABC Transporters in Drug Resistance, Metabolism, and Toxicity / Curr Drug Deliv 1 : 27 ~ 42
Hashizume T / 1998 / N-Dealkylation and hydroxylation of ebastine by human liver cytochrone P450 / Drug Metab Dispos 26 : 566 ~ 571
Fenner KS / 2009 / Drug-drug interactions mediated through P-glycoprotein : clinical relevance and in vitroin vivo correlation using digoxin as a probe drug / Clin Pharmacol
Fujii T / 1997 / Studies on the firstpass metabolism of ebastine in rats / Arzneimittelforschung 47 : 949 ~ 953
Glavinas H / 2004 / The Role of ABC Transporters in Drug Resistance, Metabolism, and Toxicity / Curr Drug Deliv 1 : 27 ~ 42
Hashizume T / 1998 / N-Dealkylation and hydroxylation of ebastine by human liver cytochrone P450 / Drug Metab Dispos 26 : 566 ~ 571
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