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KMID : 0941820130230040322
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Korean Journal of Clinical Pharmacy
2013 Volume.23 No. 4 p.322 ~ p.326
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Effect of Telmisartan on the Pharmacokinetics of Ebastine
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Baek Sang-Hoon
Park Sun-Kyoung
Jang Yoo-Jeong
Lim Mi-Sun
Kang Won-Ku
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Abstract
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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 of telmisartan (4 mg/kg, p.o.). Heparinized blood was serially taken and the plasma concentrations of ebastine and its three metabolites (hydroxyebastine, carebastine and desalkylebastine) were determined using LC-MS/MS, and their pharmacokinetic parameters 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 significantly increased 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 desalkylebastine was not detected in plasma. The systemic exposure of ebastine was significantly augmented by telmisartan, indicating that telmisartan may enhance the absorption of ebastine by blocking P-gp.
Conclusion: Although telmisartan may also partially contribute to inhibit the biotransformation to hydroxyebastine, the inhibitory action seemed to be overridden by the enhancement of absorption, because the generation of hydroxyebastine was not diminished. In spite of such interactions between telmisartan and ebastine, no clinical consequence could be expected due to no significant change of the active metabolite, carebastine.
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KEYWORD
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Telmisartan, Ebastine, Pharmacokinetics, CYP2J2, P-glycoprotein
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