We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Pharmacokinetics and toxicity of the novel oral demethylating agent zebularine in laboratory and tumor bearing dogs.
- Authors
Fulkerson, C. M.; Dhawan, D.; Jones, D. R.; Marquez, V. E.; Jones, P. A.; Wang, Z.; Wu, Q.; Klaunig, J. E.; Fourez, L. M.; Bonney, P. L.; Knapp, D. W.
- Abstract
The purpose of this study was to determine the plasma pharmacokinetics ( PK) and toxicity of zebularine, an oral cytidine analog with demethylating activity, in dogs. Plasma zebularine concentrations were determined by HPLC-MS/ MS following an oral zebularine dose of 8 or 4 mg kg−1. Plasma zebularine clearance was constant. Mean maximum concentration (Cmax) was 23 ± 4.8 and 8.6 ± 1.4 µM following 8 and 4 mg kg−1, respectively. Mean half-life was 5.7 ± 0.84 and 7.1 ± 2.1 following 8 and 4 mg kg−1, respectively. A single 8 mg kg−1 dose was well tolerated. Daily 4 mg kg−1 treatment in three laboratory dogs resulted in grade 4 neutropenia ( n = 3), grade 1 anorexia ( n = 2) and grade 1 or 2 dermatologic changes ( n = 2). All adverse events resolved with supportive care. A 4 mg kg−1 dose every 21 days was well tolerated. A follow-up dose escalation study is in progress with a lower starting dose.
- Subjects
DNA methylation; EPIGENETICS; PHARMACOKINETICS; BLOOD plasma; DEMETHYLATION
- Publication
Veterinary & Comparative Oncology, 2017, Vol 15, Issue 1, p226
- ISSN
1476-5810
- Publication type
Article
- DOI
10.1111/vco.12159