A Pilot, First-in-Human, Pharmacokinetic Study of 9cUAB30 in Healthy Volunteers

作者：Kolesar Jill M^*; Hoel Ryan; Pomplun Marcia; Havighurst Tom; Stublaski Jeanne; Wollmer Barbara; Krontiras Helen; Brouillette Wayne; Muccio Donald; Kim KyungMann; Grubbs Clinton J; Bailey Howard E

来源：Cancer Prevention Research, 2010, 3(12): 1565-1570.

DOI：10.1158/1940-6207.CAPR-10-0149

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. Cancer Prev Res; 3(12); 1565-70.

• 出版日期2010-12