Journal article
A Pilot, First-in-Human, Pharmacokinetic Study of 9cUAB30 in Healthy Volunteers
Cancer prevention research (Philadelphia, Pa.), Vol.3(12), pp.1565-1570
12/01/2010
DOI: 10.1158/1940-6207.CAPR-10-0149
PMCID: PMC3204611
PMID: 21149332
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. Cancer Prev Res; 3(12); 1565-70. (C) 2010 AACR.
Details
- Title: Subtitle
- A Pilot, First-in-Human, Pharmacokinetic Study of 9cUAB30 in Healthy Volunteers
- Creators
- Jill M. Kolesar - University of AlabamaRyan Hoel - University of AlabamaMarcia Pomplun - University of AlabamaTom Havighurst - University of AlabamaJeanne Stublaski - University of AlabamaBarbara Wollmer - University of AlabamaHelen Krontiras - University of AlabamaWayne Brouillette - University of AlabamaDonald Muccio - University of Wisconsin–MadisonKyungMann Kim - University of AlabamaClinton J. Grubbs - University of AlabamaHoward E. Bailey - University of Alabama
- Resource Type
- Journal article
- Publication Details
- Cancer prevention research (Philadelphia, Pa.), Vol.3(12), pp.1565-1570
- Publisher
- Amer Assoc Cancer Research
- DOI
- 10.1158/1940-6207.CAPR-10-0149
- PMID
- 21149332
- PMCID
- PMC3204611
- ISSN
- 1940-6207
- eISSN
- 1940-6215
- Number of pages
- 6
- Grant note
- N01CN035153 / DIVISION OF CANCER PREVENTION AND CONTROL; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) M01 RR03186 / National Cancer for Research Resources, National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30CA014520 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) M01RR003186 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) N01-CN-35153-6 / NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) National Cancer Institute's Division of Cancer Prevention, National Institutes of Health in the U.S. Department of Health and Human Services P30 CA014520- / NIH/NCI, UW Comprehensive Cancer Center Support; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 12/01/2010
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695789502771
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