A pilot, first-in-human, pharmacokinetic study of 9cUAB30 in healthy volunteers

Academic Article

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; Cmax 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. ©2010 AACR.
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    Digital Object Identifier (doi)

    Author List

  • Kolesar JM; Hoel R; Pomplun M; Havighurst T; Stublaski J; Wollmer B; Krontiras H; Brouillette W; Muccio D; Kim K
  • Start Page

  • 1565
  • End Page

  • 1570
  • Volume

  • 3
  • Issue

  • 12