Open AccessClinical Drug–Drug Interaction Potential of BFE1224, Prodrug of Antifungal Ravuconazole, Using Two Types of Cocktails in Healthy Subjects
Author(s) -
Ishii Yasuyuki,
Ito Yuko,
Matsuki Shunji,
Sanpei Kasumi,
Ogawa Osamu,
Takeda Kenji,
Schuck Edgar L.,
Uemura Naoto
Publication year - 2018
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12557
Subject(s) - drug , prodrug , pharmacology , medicine , antifungal , drug interaction , antifungal drugs , dermatology
Abstract BFE1224, prodrug of ravuconazole, is a novel, once‐daily, oral, triazole antifungal drug, and currently in development for the treatment of onychomycosis. The clinical drug–drug interaction (DDI) potential of BFE1224 with cytochrome P450 (CYP) and transporter was assessed by using two types of cocktails in healthy subjects in separate clinical studies. The CYP and transporter cocktails consisted of caffeine/tolbutamide/omeprazole/dextromethorphan/midazolam used in study 1 and digoxin/rosuvastatin used in study 2. In addition, repaglinide was separately administered to the same subjects in study 2. There were no major effects on the pharmacokinetics of CYP and transporter substrates, except for an approximate threefold increase in midazolam exposure after oral administration of BFE1224. The clinical DDIs of BFE1224 were mild for CYP3A and minor for other major CYPs (CYP1A2/2C8/2C9/2C19/2D6) as well as those of P‐glycoprotein (P‐gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, and OATP1B3.