title: A pilot, first-in-human, pharmacokinetic study of 9cUAB30 in healthy volunteers.
abstract: 9cUAB30 is a synthetic analog of 9-cis-retinoic acid with chemopreventive activity in cell lines and in animal models. The purpose of this first-in-human evaluation of 9cUAB30 was to evaluate the single-dose pharmacokinetic profile and toxicity of the compound in healthy volunteers at 3 dose levels. This study enrolled 14 patients to receive a single dose of 5, 10, or 20 mg of 9cUAB30. Plasma and urine samples were collected to assess 9cUAB30 concentrations by a validated LC/MS MS method. 9cUAB30 was well tolerated, with 1 patient experiencing grade 2 toxicity and no grade 3 or 4 toxicities reported. T(max) occurred approximately 3 hours after dose administration with the plasma half-life ranging from 2.79 to 7.21 hours. AUC increased linearly across the examined dose range of 5 to 20 mg; C(max) was proportional to the log of the dose. The plasma clearance ranged from 25 to 39 L/h compared to the renal clearance which ranged from 0.018 to 0.103 L/h. 9cUAB30 has a favorable toxicity and pharmacokinetic profile, with oral availability and primarily hepatic metabolism. Further dose ranging studies with once a day dosing are underway.
authors.affiliation: University of Wisconsin, Madison, WI 53792, USA. jmkolesar@pharmacy.wisc.edu
authors.forename: Jill M
authors.initials: JM
authors.lastname: Kolesar
authors.forename: Ryan
authors.initials: R
authors.lastname: Hoel
authors.forename: Marcia
authors.initials: M
authors.lastname: Pomplun
authors.forename: Tom
authors.initials: T
authors.lastname: Havighurst
authors.forename: Jeanne
authors.initials: J
authors.lastname: Stublaski
authors.forename: Barbara
authors.initials: B
authors.lastname: Wollmer
authors.forename: Helen
authors.initials: H
authors.lastname: Krontiras
authors.forename: Wayne
authors.initials: W
authors.lastname: Brouillette
authors.forename: Donald
authors.initials: D
authors.lastname: Muccio
authors.forename: Kyungmann
authors.initials: K
authors.lastname: Kim
authors.forename: Clinton J
authors.initials: CJ
authors.lastname: Grubbs
authors.forename: Howard E
authors.initials: HE
authors.lastname: Bailey
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D010865:Pilot Projects; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: D005231:Fatty Acids, Unsaturated; D009281:Naphthalenes; C112106:UAB 30