title: Efinaconazole: Developmental and reproductive toxicity potential of a novel antifungal azole.
abstract: Efinaconazole is a new triazole antifungal for topical treatment of onychomycosis. The reproductive and developmental toxicity of efinaconazole was characterized in fertility and early embryonic development (rat), embryo-fetal development (rat and rabbit), and peri/post-natal development (rat) studies in accordance with current ICH guidances. In the fertility study, maternal reproductive toxicity was noted as estrous cycle prolongation (NOAEL=5mg/kg/day) but there were no male reproductive effects even in the presence of paternal toxicity (NOAEL=25mg/kg/day). Rat embryo-fetal and perinatal pup lethality was the most sensitive (NOAEL=5mg/kg/day) efinaconazole developmental toxicity and was noted at maternally toxic doses. Efinaconazole did not affect rabbit embryo-fetal development at maternally toxic doses (NOAEL=10mg/kg/day). No malformations were induced by efinaconazole in rats or rabbits. When compared with systemic exposures observed in onychomycosis patients, embryo-fetal toxicity in rats was noted at high (>100-fold) multiples of systemic exposure.
authors.affiliation: Dow Pharmaceutical Sciences, A Division of Valeant Pharmaceuticals North America, LLC, 1330 Redwood Way, Petaluma, CA 94594, USA. Electronic address: toxclarity@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Glynn
authors.affiliation: Dow Pharmaceutical Sciences, A Division of Valeant Pharmaceuticals North America, LLC, 1330 Redwood Way, Petaluma, CA 94594, USA. Electronic address: wjo@dowpharmsci.com.
authors.forename: W
authors.initials: W
authors.lastname: Jo
authors.affiliation: Kaken Pharmaceutical Co., Ltd., 301 Gensuke, Fujieda, Shizuoka, Japan. Electronic address: minowa_kenji@kaken.co.jp.
authors.forename: K
authors.initials: K
authors.lastname: Minowa
authors.affiliation: Kaken Pharmaceutical Co., Ltd., 301 Gensuke, Fujieda, Shizuoka, Japan. Electronic address: sanada_hisakazu@kaken.co.jp.
authors.forename: H
authors.initials: H
authors.lastname: Sanada
authors.affiliation: Kaken Pharmaceutical Co., Ltd., 301 Gensuke, Fujieda, Shizuoka, Japan. Electronic address: nejishima_hiroaki@kaken.co.jp.
authors.forename: H
authors.initials: H
authors.lastname: Nejishima
authors.affiliation: Kaken Pharmaceutical Co., Ltd., 301 Gensuke, Fujieda, Shizuoka, Japan. Electronic address: matsuuchi_hiroyuki@kaken.co.jp.
authors.forename: H
authors.initials: H
authors.lastname: Matsuuchi
authors.affiliation: Kaken Pharmaceutical Co., Ltd., 301 Gensuke, Fujieda, Shizuoka, Japan. Electronic address: okamura_hayao@kaken.co.jp.
authors.forename: H
authors.initials: H
authors.lastname: Okamura
authors.affiliation: Dow Pharmaceutical Sciences, A Division of Valeant Pharmaceuticals North America, LLC, 1330 Redwood Way, Petaluma, CA 94594, USA. Electronic address: rpillai@dowpharmsci.com.
authors.forename: R
authors.initials: R
authors.lastname: Pillai
authors.affiliation: Dow Pharmaceutical Sciences, A Division of Valeant Pharmaceuticals North America, LLC, 1330 Redwood Way, Petaluma, CA 94594, USA. Electronic address: lmutter@dowpharmsci.com.
authors.forename: L
authors.initials: L
authors.lastname: Mutter
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000935:Antifungal Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects*; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D005313:Fetal Death; D008297:Male; D011817:Rabbits; D051381:Rats; D012098:Reproduction / Q000187:drug effects*; D014230:Triazoles / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C431707:efinaconazole
keywords: Antifungal; CYP51; Efinaconazole; Embryolethal; Lanosterol 14α demethylase; Propylene glycol; Triazole