title: Tavaborole, a Novel Boron-Containing Small Molecule Pharmaceutical Agent for Topical Treatment of Onychomycosis: I. Reproductive and Developmental Toxicity Studies.
abstract: Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. As part of the nonclinical development program, reproductive and developmental toxicity studies were conducted (rat oral fertility and early embryonic development, rat (oral) and rabbit (dermal) embryo-fetal development). There were no effects on fertility or reproductive performance at doses up to 300 mg/kg/d (107 times the maximum recommended human dose [MRHD] based on mean area under the plasma concentration-time curve comparisons). In the rat embryo-fetal development toxicity studies, teratogenicity was not observed at doses up to 100 mg/kg/d (29 times the MRHD). However, several treatment-related skeletal malformations and variations were observed at 300 mg/kg/d (570 times the MRHD). In rabbit embryo-fetal development toxicity studies dosed via oral or dermal administration, the no observable adverse effect level for maternal toxicity and embryo-fetal toxicity was 50 mg/kg/d (16 times the MRHD) and 5% (26 times the MRHD), respectively.
authors.affiliation: Anacor Pharmaceuticals, Inc, Palo Alto, CA, USA vciaravino@anacor.com.
authors.forename: Vic
authors.initials: V
authors.lastname: Ciaravino
authors.affiliation: Anacor Pharmaceuticals, Inc, Palo Alto, CA, USA.
authors.forename: Dina
authors.initials: D
authors.lastname: Coronado
authors.affiliation: MPI Research, Mattawan, MI, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Lanphear
authors.affiliation: Charles River Laboratories, Horsham, PA, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Hoberman
authors.affiliation: Anacor Pharmaceuticals, Inc, Palo Alto, CA, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Chanda
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000831:Animals, Newborn; D000935:Antifungal Agents / Q000627:therapeutic use / Q000633:toxicity; D001895:Boron / Q000627:therapeutic use / Q000633:toxicity*; D001896:Boron Compounds / Q000627:therapeutic use* / Q000633:toxicity*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use* / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D047109:Fetal Development / Q000187:drug effects; D008297:Male; D014009:Onychomycosis / Q000188:drug therapy*; D011817:Rabbits; D051381:Rats; D012098:Reproduction / Q000187:drug effects*; D018675:Toxicity Tests
chemical_list: D000935:Antifungal Agents; D001896:Boron Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; C512998:tavaborole; D001895:Boron
keywords: developmental toxicity; reproductive development; tavaborole; teratology