Pharmacokinetics of the H1-receptor antagonist ebastine and its active metabolite carebastine in healthy subjects.
Pharmacokinetics of ebastine (CAS 90729-43-4), a histamine H1-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 90729-42-3), 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 Cmax 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 pharmacokinetics of ebastine and carebastine. Plasma concentration of carebastine reached the steady state on day 4. The Cmax (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.
Yamaguchi
T
T
Department of Pharmacokinetics, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Hashizume
T
T
Matsuda
M
M
Sakashita
M
M
Fujii
T
T
Sekine
Y
Y
Nakashima
M
M
Uematsu
T
T
D000328:Adult; D002090:Butyrophenones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D005502:Food; D006207:Half-Life; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D011485:Protein Binding
D002090:Butyrophenones; D006634:Histamine H1 Antagonists; D010880:Piperidines; C058251:carebastine; C058249:ebastine