Publication: Dichloroacetate for lactic acidosis in severe malaria: A pharmacokinetic and pharmacodynamic assessment
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Issued Date
1994-01-01
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ISSN
00260495
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2-s2.0-0027941420
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Mahidol University
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SCOPUS
Bibliographic Citation
Metabolism. Vol.43, No.8 (1994), 974-981
Suggested Citation
S. Krishna, W. Supanaranond, S. Pukrittayakamee, D. Karter, Y. Supputamongkol, T. M.E. Davis, P. A. Holloway, N. J. White Dichloroacetate for lactic acidosis in severe malaria: A pharmacokinetic and pharmacodynamic assessment. Metabolism. Vol.43, No.8 (1994), 974-981. doi:10.1016/0026-0495(94)90177-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/9537
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Title
Dichloroacetate for lactic acidosis in severe malaria: A pharmacokinetic and pharmacodynamic assessment
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Abstract
Lactic acidosis and hypoglycemia are potentially lethal complications of falciparum malaria. We have evalua ted the pharmacokinetics and pharmacodynamics of dichloroacetate ([DCA], 46 mg/kg infused over 30 minutes), a stimulant of pyruvate dehydrogenase and a potential treatment for lactic acidosis, in 13 patients with severe malaria and compared the physiological and metabolic responses with those of a control group of patients (n = 32) of equivalent disease severity. The mean ± SD peak postinfusion level of DCA was 78 ± 23 mg/L, the total apparent volume of distribution was 0.75 ± 0.35 L/kg, and systemic clearance was 0.32 ± 0.16 L/kg/h. Geometric mean (range) venous lactate concentrations in control and DCA recipients before treatment were 4.5 (2.1 to 19.5) and 5.5 (2 to 15.4) mmol/L, respectively (P > .1). A single DCA infusion decreased lactate concentrations from baseline by a mean of 27% after 2 hours, 40% after 4 hours, and 41% after 8 hours, compared with decreases of 5%, 6%, and 16%, respectively, in controls (P = .032). These changes were preceded by rapid and marked decreases in pyruvate concentrations. Arterial pH increased from 7.328 to 7.374 (n = 10, P < .02) 2 hours after the infusion. Hypoglycemia was prevented by infusing glucose at 3 mg/kg/min. There was no clinical, electrocardiographic, or laboratory evidence of toxicity. These results suggest that DCA should be investigated further as an adjunctive therapy for severe malaria. © 1994.