Literature DB >> 1878534

Disposition and pharmacodynamics of dichloroacetate (DCA) and oxalate following oral DCA doses.

S H Curry1, A Lorenz, P I Chu, M Limacher, P W Stacpoole.   

Abstract

Healthy volunteers received intravenous and/or oral doses of sodium dichloroacetate (DCA) in various single and multiple dose regimens. A crossover bioavailability study proved abortive because second and subsequent doses showed significantly longer terminal elimination half-lives (means 3.64 h and 9.9 h, respectively) than was the case for initial doses (1.58 h). A parallel bioavailability comparison failed to show that oral doses were significantly different from 100 per cent bioavailability (AUCoral, 604 micrograms h-1 ml-1; AUCi.v., 489 micrograms h-1 ml-1). The time required to elapse between individual doses, in order to prevent second doses having relatively long half-life values, varied in different individuals from 1 week to greater than 3 months. No cardiac or central nervous system effects were recorded by echocardiography and digit symbol substitution tests, respectively. The mean renal clearance of DCA was 42.9 ml h-1. No differences were observed in DCA kinetics between male and female subjects.

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Year:  1991        PMID: 1878534     DOI: 10.1002/bdd.2510120507

Source DB:  PubMed          Journal:  Biopharm Drug Dispos        ISSN: 0142-2782            Impact factor:   1.627


  16 in total

Review 1.  Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1.

Authors:  Margaret O James; Stephan C Jahn; Guo Zhong; Marci G Smeltz; Zhiwei Hu; Peter W Stacpoole
Journal:  Pharmacol Ther       Date:  2016-10-19       Impact factor: 12.310

2.  DCA promotes progression of neuroblastoma tumors in nude mice.

Authors:  Benedikt Feuerecker; Christof Seidl; Sabine Pirsig; Gernot Bruchelt; Reingard Senekowitsch-Schmidtke
Journal:  Am J Cancer Res       Date:  2015-01-15       Impact factor: 6.166

3.  Model Informed Dose Optimization of Dichloroacetate for the Treatment of Congenital Lactic Acidosis in Children.

Authors:  Naveen Mangal; Margaret O James; Peter W Stacpoole; Stephan Schmidt
Journal:  J Clin Pharmacol       Date:  2017-09-15       Impact factor: 3.126

4.  A Mechanism-Based Pharmacokinetic Enzyme Turnover Model for Dichloroacetic Acid Autoinhibition in Rats.

Authors:  Yu Jiang; Gary Milavetz; Margaret O James; Guohua An
Journal:  J Pharm Sci       Date:  2017-02-03       Impact factor: 3.534

5.  Toxicity and carcinogenicity of the water disinfection byproduct, dibromoacetic acid, in rats and mice.

Authors:  Ronald L Melnick; Abraham Nyska; Paul M Foster; Joseph H Roycroft; Grace E Kissling
Journal:  Toxicology       Date:  2006-12-08       Impact factor: 4.221

6.  Non-Hodgkin's Lymphoma Reversal with Dichloroacetate.

Authors:  Dana F Flavin
Journal:  J Oncol       Date:  2010-09-16       Impact factor: 4.375

7.  Age-dependent kinetics and metabolism of dichloroacetate: possible relevance to toxicity.

Authors:  Albert L Shroads; Xu Guo; Vaishali Dixit; Hui-Ping Liu; Margaret O James; Peter W Stacpoole
Journal:  J Pharmacol Exp Ther       Date:  2007-12-20       Impact factor: 4.030

8.  Targeting unique metabolic properties of breast tumor initiating cells.

Authors:  Weiguo Feng; Andrew Gentles; Ramesh V Nair; Min Huang; Yuan Lin; Cleo Y Lee; Shang Cai; Ferenc A Scheeren; Angera H Kuo; Maximilian Diehn
Journal:  Stem Cells       Date:  2014-07       Impact factor: 6.277

9.  Physiologically based pharmacokinetic modeling of dibromoacetic acid in F344 rats.

Authors:  Jessica L Matthews; Irvin R Schultz; Michael R Easterling; Ronald L Melnick
Journal:  Toxicol Appl Pharmacol       Date:  2010-01-04       Impact factor: 4.219

Review 10.  Role of dichloroacetate in the treatment of genetic mitochondrial diseases.

Authors:  Peter W Stacpoole; Tracie L Kurtz; Zongchao Han; Taimour Langaee
Journal:  Adv Drug Deliv Rev       Date:  2008-07-04       Impact factor: 15.470

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