Superfund Research Program

Peter W. Stacpoole

University of Florida
P.O. Box 100226
Gainesville, Florida 32610
Phone: 352-392-2321
Fax: 352-846-0990
Email: Stacpool@gcrc.ufl.edu

Projects

• University of Florida: Dichloroacetate Kinetics, Metabolism and Human Toxicology (1995 - 2000)
• University of Florida: Pharmacology of Trichloroethylene Metabolites (2000-2006)

Research Briefs

• 25 - Comparative Metabolism Studies of Dichloroacetate

Publications

2018

• Mangal N, James MO, Stacpoole PW, Schmidt S. 2018. Model informed dose optimization of dichloroacetate for the treatment of congenital lactic acidosis in children. J Clin Pharmacol 58:212-220. doi:10.1002/jcph.1009 PMID:28914978

2008

• Guo X, James MO, Stacpoole PW. 2008. Age-dependent kinetics and metabolism of dichloroacetate: possible relevance to toxicity. J Pharmacol Exp Ther 324(3):1163-71. PMID:18096758

2007

• Felitsyn NM, Stacpoole PW, Notterpek-Fletcher L. 2007. Dichloroacetate causes reversible demyelination in vitro: potential mechanism for its neuropathic effect. J Neurochem 100(2):429-436. PMID:17241159

2006

• Jia M, Coats BS, Chandha M, Frentzen B, Perez-Rodriguez J, Chadik PA, Yost RA, Henderson GN, Stacpoole PW. 2006. Human kinetics of orally and intravenously administered low-dose 1,2-(13)C-dichloroacetate. Prenat Diagn 46(12):1449-1459. doi:10.1177/0091270006292627 PMID:17101744
• Stickler D, Valenstein E, Neiberger RE, Perkins LA, Carney PR, Shuster JJ, Theriaque DW, Stacpoole PW. 2006. Peripheral neuropathy in genetic mitochondrial diseases. Neurology 34(2):127-131. doi:10.1016/j.pediatrneurol.2005.08.006 PMID:16458825

2004

• Dixit VS, Guo X, James MO, Henderson GN, Stacpoole PW. 2004. Chronic exposure to environmental levels of dichloroacetate decreases glutathione s-trasferase pi activity and expression. In: Proceedings of the 7^th International ISSX (Internation Soceity of the Study of Xenobiotics) Meeting, August 29, September 2. Vancouver, Cameroon.
• Duncan GE, Perkins LA, Theriaque DW, Neiberger RE, Stacpoole PW. 2004. Dichloroacetate therapy attenuates the blood lactate response to submaximal exercise in patients with defects in mitochondrial energy metabolism. J Clin Endocrinol Metab 89(4):1733-1738. PMID:15070938
• Felitsyn NM, Henderson GN, James MO, Stacpoole PW. 2004. Liquid chromatography-tandem mass spectrometry method for the simultaneous determination of delta-ALA, tyrosine and creatinine in biological fluids. Clin Chim Acta 350(1-2):219-230. PMID:15530481
• Guo X, Dixit VS, Henderson GN, James MO, Stacpoole PW. 2004. Induction of glutathione Stransferasezeta (GSTz) protein expression by flavones. In: Proceedings of the 7^th International ISSX (Internation Soceity of the Study of Xenobiotics) Meeting, August 29, September 2. Vancouver, Cameroon.
• Jia M, Stacpoole PW, Chadik PA, Yost RA, Chadha M, Coats BS, Henderson GN. 2004. Human levels of haloacetic acids from chlorinated drinking water. In: Proceedings of the 7^th International ISSX (Internation Soceity of the Study of Xenobiotics) Meeting, August 29, September 2. Vancouver, Cameroon.
• Shroads AL, Henderson GN, Cheung J, James MO, Stacpoole PW. 2004. Unified gas chromatographic-mass spectrometric method for quantitating tyrosine metabolites in urine and plasma. J Chromatogr B Analyt Technol Biomed Life Sci 808(2):153-161. PMID:15261808

2003

• Agbenyega T, Planche T, Bedu-Addo G, Ansong D, Owusu-Ofori A, Bhattaram VA, Nagaraja NV, Shroads AL, Henderson GN, Hutson AD, Derendorf H, Krishna S, Stacpoole PW. 2003. Population kinetics, efficacy, and safety of dichloroacetate for lactic acidosis due to severe malaria in children. Prenat Diagn 43(4):386-396. PMID:12723459
• Ammini CV, Fernandez-Canon J, Shroads AL, Cornett R, Cheung J, James MO, Henderson GN, Grompe M, Stacpoole PW. 2003. Pharmacologic or genetic ablation of maleylacetoacetate isomerase increases levels of toxic tyrosine catabolites in rodents. Biochem Pharmacol 66(10):2029-2038. PMID:14599561
• Ammini CV, Stacpoole PW. 2003. "Biotransformation, Toxicology and Pharmacogenomics of Dichloroacetate," In Natural Production of Organohalogen Compounds. Chapter Vol. 3 Part P in: The Handbook of Environmental Chemistry. Springer Verlag, Heidelberg, Germany. pp.215-234.
• Constantinidis I, Simpson NE, Han Z, Harrison J, Stacpoole PW. 2003. Probing mitochondrial disorders through NMR spectroscopy. In: Proceedings of the International Congress of Inborn Errors of Metabolism, September 2-6. Brisbane, Queensland, Australia.
• Duncan GE, Perkins LA, Theriaque DW, Neiberger RE, Stacpoole PW. 2003. Dichloroacetate improves parameters of aerobic function in patients with defects in mitochondrial energy metabolism. In: Proceedings of the American College of Sports Medicine, 50th Annual Meeting, May 28-31. San Francisco, CA.
• Duncan GE, Perkins LA, Theriaque DW, Neiberger RE, Stacpoole PW. 2003. Dichloroacetate improves parameters of aerobic function in patients with defects in mitochondrial energy metabolism. In: Proceedings of the International Congress of Inborn Errors of Metabolism, September 2-6. Brisbane, Queensland, Australia.
• Garrett TJ, Guo X, Stacpoole PW, Yost RA. 2003. Characterization of the lipid content in peripheral nerve tissue from rats exposed to dichloroacetate. In: Proceedings of the 51^st ASMS Annual Conference on Mass Spectrometry and Allied Topics, June 10. Montreal, Canada.
• Guo X, Henderson GN, James MO, Stacpoole PW. 2003. Time course of inhibition and recovery of hepatic glutathione s-transferase zeta (GSTx) by dichloroacetate (DCA). In: Proceedings of the 8th European ISSX Meeting, April 27, May 1. Dijon, France.
• Jia M, Wu WW, Yost MG, Chadik PA, Stacpoole PW, Henderson GN. 2003. Simultaneous determination of trace levels of nine haloacetic acids in biological samples as their pentafluorobenzyl derivatives by gas chromatography/tandem mass spectrometry in electron capture negative ion chemical ionization mode. Anal Chem 75(16):4065-4080. PMID:14632119
• Simpson NE, Han Z, Harrison J, Rocca J, Stacpoole PW, Constantinidis I. 2003. Probing mitochondrial disorders through 13C and 31P NMR analysis of extracts. In: Proceedings of the International Society of Magnetic Resonance in Medicine, 11th Annual Scientific Meeting, May 10-16. Toronto, Canada.
• Stacpoole PW. 2003. Congenital lactic acidosis. In: The NORD Guide to Rare Disorders. Lippincott, Williams and Wilkins, pp.462-464.
• Stacpoole PW, Guo X, Shroads AL, Shelton GD, Calcutt NA, James MO, Eskin TA, Henderson GN, Notterpek-Fletcher L. 2003. Mechanisms of dichloroacetate-induced peripheral neuropathy in patients with mitochondrial diseases. In: Proceedings of the 12th North American ISSX (Internation Soceity of the Study of Xenobiotics) Meeting, October 12-16. Providence, RI.
• Stacpoole PW, Nagaraja NV, Hutson AD. 2003. Efficacy of dichloroacetate as a lactate lowering drug. Prenat Diagn 43(7):683-691. PMID:12856382

2002

• Neiberger RE, George JC, Perkins LA, Theriaque DW, Hutson AD, Stacpoole PW. 2002. Renal manifestations of congenital lactic acidosis. American Journal of Kidney Diseases 39(1):12-23. PMID:11774096
• Stacpoole PW. 2002. Dichloroacetate treatment of congenital lactic acidosis: preliminary outcome results of the DCA/CLA clinical trial. In: Society for Inherited Metabolic Disorders Annual Meeting, March 3-6. Pacific Grove, CA.

2001

• Ammini CV, Shroads AL, Cornett R, Henderson GN, James MO, Stacpoole PW. 2001. Perturbation of tyrosine catabolism by dichloroacetate: a putative pathway for toxicity. In: Proceedings of the 6^th International ISSX (International Society for the Study of Xenobiotics) Meeting, October 7-11. Munich, Germany.
• Stacpoole PW. 2001. Human kinetics, biotransformation and toxicology of dichloroacetate. In: Proceedings of the 2^nd International Conference of Naturally Produced Organohalogens. September 30 - October 4. Heidelberg, Germany.
• Weber TA, Antognetti MR, Stacpoole PW. 2001. Caveats when considering ketogenic diets for the treatment of pyruvate dehydrogenase complex deficiency. J Pediatr 138(3):390-395. PMID:11241048

2000

• Cornett-Mueller R, James MO, Ally A, Henderson GN, Cheung J, Ammini CV, Stacpoole PW, Shroads AL. 2000. Involvement of the tyrosine catabolic pathway in the inhibition of DCA metabolism. Society of Toxicology
• James MO, Cornett R, Henderson GN, Shroads AL, Stacpoole PW. 2000. Destruction of glutathione S-transferase zeta protein by dichloroacetic acid treatment. British Pharmacological Society 131(Suppl.5):104P.
• Neiberger RE, George JC, Perkins LA, Theriaque DW, Hutson AD, Stacpoole PW. 2000. Renal functional abnormalities in children with congenital lactic acidosis. J Am Soc Nephrol M1:159A.

1999

• Cornett R, James MO, Henderson GN, Ally A, Cheung J, Shroads AL, Stacpoole PW. 1999. Inhibition of dichloroacetate metablolism by z-4,6-dioxohep-2-enoic acid (Maleylacetone), a natural substrate for GST-zeta. ISSX Proceedings 15:194A.
• Cornett R, James MO, Henderson GN, Cheung J, Shroads AL, Stacpoole PW. 1999. Inhibition of glutathione S-transferase zeta and tyrosine metabolism by dichloroacetate: a potential unifying mechanism for its altered biotransformation and toxicity. Biochem Biophys Res Commun 262(3):752-756. PMID:10471397
• Stacpoole PW, Bunch ST, Neiberger RE, Perkins LA, Quisling R, Hutson AD, Greer M. 1999. The importance of cerebrospinal fluid lactate in the evaluation of congenital lactic acidosis. J Pediatr 134(1):99-102. PMID:9880457
• Yan Z, Henderson GN, James MO, Stacpoole PW. 1999. Determination of chloral hydrate metabolites in human plasma by gas chromatography-mass spectrometry. J Pharm Biomed Anal 19(3-4):309-318. PMID:10704096

1998

• James MO, Yan Z, Cornett R, Jayanti VK, Henderson GN, Davydova N, Katovich MK, Pollock B, Stacpoole PW. 1998. Pharmacokinetics and metabolism of [¹⁴C] dichloroacetate (DCA) in the male Sprague-Dawley rat: identification of the glycine conjugates, including hippuric, as urinary metabolites of DCA. Drug Metab Dispos 26(11):1134-1143.
• Pavlakis SG, Kingsley PB, Kaplan GP, Stacpoole PW, O'Shea M, Lustbader D. 1998. Magnetic resonance spectroscopy use in monitoring MELAS treatment. Arch Neurol 55:849-852. PMID:9626777
• Stacpoole PW. 1998. Dichloroacetate treatment of congenital lactic acidosis: pros and cons. Japanese Journal for Inherited Metabolic Diseases 14:9-14.
• Stacpoole PW, Henderson GN, Yan Z, Cornett R, James MO. 1998. Pharmokinetics, metabolism and toxicology of dichloroacetate. J Mol Biol 30(3):499-539. PMID:9710704
• Stacpoole PW, Henderson GN, Yan Z, James MO. 1998. Clinical pharmacology and toxicology of dichloroacetate. Environ Health Perspect 106(4):989-994. PMID:9703483

1997

• Henderson GN, Yan Z, James MO, Davydova N, Stacpoole PW. 1997. Kinetics and metabolism of chloral hydrate in children: identification of dichloroacetate as a metabolite. Biochem Biophys Res Commun 235(3):695-698. PMID:9207222
• James MO, Cornett R, Yan Z, Henderson GN, Stacpoole PW. 1997. Glutathione-dependent conversion to glyoxylate, a major pathway of dichloroacetate biotransformation in hepatic cytosol from humans and rats, is reduced in dichloroacetate-treated rats. Drug Metab Dispos 25(11):1223-1227. PMID:9351896
• Stacpoole PW, Barnes CL, Hurbanis MD, Cannon SL, Kerr DS. 1997. Treatment of congenital lactic acidosis with dichloroacetate. Archives of Disease in Childhood 77(6):535-541. PMID:9496194
• Yan Z, Henderson GN, James MO, Stacpoole PW. 1997. Determination of dichloroacetate and its metabolites in human plasma by gas chromatography-mass spectrometry. Journal of Chromatographic Science 703(1-2):75-84. PMID:9448064

1995

• James MO, Jayanti VK, Henderson GN, Stacpoole PW. 1995. In vivo and in vitro metabolism of [14C]-dichloroacetic acid (DCA) in the male Sprague-Dawley rat. Environ Health Perspect 15:261.

1985

• Shroads AL, Coats BS, McDonough CW, Langaee T, Stacpoole PW. 1985. The impact of maternal serum alpha fetoprotein screening on open neural tube defect births in north-east Scotland. Prenat Diagn 5(1):15-19. PMID:2579374