Presented as a poster at the 52nd Annual Meeting of the Society of Toxicology March 10–14, 2012 in San Antonio, TX, USA.
Pharmacokinetics of Oral Dichloroacetate in Dogs
Article first published online: 13 SEP 2013
© 2013 Wiley Periodicals, Inc.
Journal of Biochemical and Molecular Toxicology
Volume 27, Issue 12, pages 522–525, December 2013
How to Cite
Maisenbacher, H. W., Shroads, A. L., Zhong, G., Daigle, A. D., Abdelmalak, M. M., Samper, I. S., Mincey, B. D., James, M. O. and Stacpoole, P. W. (2013), Pharmacokinetics of Oral Dichloroacetate in Dogs. J. Biochem. Mol. Toxicol., 27: 522–525. doi: 10.1002/jbt.21518
Contract Grant Sponsor: University of Florida College of Veterinary Medicine.
The authors have no financial interests to disclose.
- Issue published online: 2 DEC 2013
- Article first published online: 13 SEP 2013
- Manuscript Accepted: 20 JUL 2013
- Manuscript Revised: 1 JUL 2013
- Manuscript Received: 17 MAY 2013
- University of Florida College of Veterinary Medicine
- Drug Development;
- Mitochondrial Diseases
We characterized the pharmacokinetics and dynamics of dichloroacetate (DCA), an investigational drug for mitochondrial diseases, pulmonary arterial hypertension, and cancer. Adult Beagle dogs were orally administered 6.25 mg/kg q12h DCA for 4 weeks. Plasma kinetics was determined after 1, 14, and 28 days. The activity and expression of glutathione transferase zeta 1 (GSTZ1), which biotransforms DCA to glyoxylate, were determined from liver biopsies at baseline and after 27 days. Dogs demonstrate much slower clearance and greater inhibition of DCA metabolism and GSTZ1 activity and expression than rodents and most humans. Indeed, the plasma kinetics of DCA in dogs is similar to humans with GSTZ1 polymorphisms that confer exceptionally slow plasma clearance. Dogs may be a useful model to further investigate the toxicokinetics and therapeutic potential of DCA.