Itraconazole and rifampin alter significantly the disposition and antihistamine effect of ebastine and its metabolites in healthy participants.
The present study was performed to elucidate the effects of itraconazole and rifampin on the pharmacokinetics and pharmacodynamics of ebastine, a nonsedative H1 receptor antagonist. In a 3-way crossover sequential design with 2-week washouts, 10 healthy participants were pretreated with itraconazole for 6 days, rifampin for 10 days, or neither. After oral administration of 20 mg ebastine, blood and urine samples were collected for 72 and 24 hours, respectively, and histamine-induced wheal and flare reactions were measured to assess the antihistamine response for 12 hours. Itraconazole pretreatment decreased the oral clearance of ebastine to 10% (P < .001) and increased the AUC(infinity) of the active metabolite, carebastine, by 3-fold (P < .001). On the other hand, rifampin pretreatment decreased the AUC(infinity) of carebastine to 15% (P < .001), with an enormous reduction in the oral bioavailability of ebastine and significantly reduced histamine-induced skin reactions. From these results, the disposition of ebastine and carebastine seems to be significantly altered by coadministration of itraconazole or rifampin. The antihistamine response after ebastine dosing would be decreased following rifampin pretreatments.
Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, South Korea.
Ji-Hong
JH
Shon
Chang-Woo
CW
Yeo
Kwang-Hyeon
KH
Liu
Sang-Seop
SS
Lee
In-Jun
IJ
Cha
Jae-Gook
JG
Shin
D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology; D002090:Butyrophenones / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000009:adverse effects; D006634:Histamine H1 Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000139:chemically induced / Q000188:drug therapy; D017964:Itraconazole / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012293:Rifampin / Q000494:pharmacology*; D012867:Skin / Q000276:immunology; D055815:Young Adult
D000935:Antifungal Agents; D002090:Butyrophenones; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D010880:Piperidines; D017964:Itraconazole; C058251:carebastine; D006632:Histamine; C058249:ebastine; D012293:Rifampin