Pharmacokinetics of the H1-receptor antagonist ebastine and its active metabolite carebastine in healthy subjects
Yamaguchi, T.; Hashizume, T.; Matsuda, M.; Sakashita, M.; Fujii, T.; Sekine, Y.; Nakashima, M.; Uematsu, T.
Arzneimittel-Forschung 44(1): 59-64
1994
ISSN/ISBN: 0004-4172 PMID: 7907873 Document Number: 424941
Pharmacokinetics of ebastine (CAS 90729-43-4), a histamine H-1-receptor antagonist, was evaluated in healthy male volunteers. The subjects were given single oral doses of 5, 10, 20 and 40 mg of ebastine (5 or 6 subjects) and repeated oral doses of 20 mg once daily for 7 days (6 subjects). Administration of ebastine resulted in a negligible level of the unchanged drug in plasma and urine. Mean plasma concentration of carebastine (CAS 90729-423), an active carboxylated metabolite, reached maximum levels of 40, 112, 195 and 388 ng/ml at 4-6 h after single oral administration of ebastine at doses of 5, 10, 20 and 40 mg, respectively. Plasma levels of carebastine showed a first-order decrease with apparent half-lives of 13.8 to 15.3 h. The C-max and AUC of carebastine increased in proportion to the dose. Urinary excretion of carebastine during 72 h after single administration accounted for 1.3-1.8% of the dose. Food intake did not affect the pharmacokinetics and gastrointestinal absorption of ebastine. Repeated administrations of ebastine once daily for 7 days did not cause any change in the parmacokinetics of ebastine and carebastine. Plasma concentration of carebastine reached the steady state on day 4. The C-max (360-396 ng/ml) was 1.6- to 1.7-fold greater than that after the first administration (229 ng/ml). These results strongly suggest that carebastine is responsible for the antihistamine activity after administration of ebastine.