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PI‐8
Author(s) -
Shon J.,
Yeo C.,
Liu K.,
Lee S.,
Cha I.,
Shin J.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.029
Subject(s) - itraconazole , pharmacodynamics , pharmacokinetics , pharmacology , medicine , antifungal , dermatology
BACKGROUND Ebastine, a nonsedative H 1 receptor antagonist, is completely metabolized to the dealkylated metabolite and carebastine, an active metabolite via hydroxylation (M‐OH). The conversion of M‐OH to carebastine and Des‐BP pathway are mainly catalyzed by CYP3A4, whereas the oxidation of ebastine to M‐OH is exclusively mediated by CYP2J2. AIMS To evaluate the effect of itraconazole and rifampin on the PK and PD of ebastine in relation to CYP2J2*8 genotype. METHODS In open, 3‐way crossover with a 2‐week washout, 4 healthy subjects with wild type and 3 with heterozygous mutation for CYP2J2*8 were pretreated with itraconazole for 6 days, rifampin for 10 days, or not. A single oral dose of 20 mg ebastine was administered to subjects and blood to 72hrs and urine to 24hrs were collected. Histamine‐induced wheal and flare reactions were measured to assess the effects on the antihistamine response to 12hrs. RESULTS The PK parameters of ebastine and active metabolite, carebastine, showed statistically significant change by pretreatment with itraconazole and rifampin. Itraconazole enhanced markedly the ebastine's inhibitory effect against histamine‐induced skin reactions and rifampin pretreatment decreased that. CONCLUSION Itraconazole and rifampin pretreatment significantly altered the disposition and antihistamine effect of ebastine and carebastine in human. However, the genotype of CYP2J2*8 seems to have little effect on those even in the inhibited and induced state of CYP3A4. Clinical Pharmacology & Therapeutics (2005) 79 , P9–P9; doi: 10.1016/j.clpt.2005.12.029