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Acta Trop. 1988 Sep;45(3):217-24.

Plasma concentrations of sulfadoxine in healthy and malaria infected Thai subjects.

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1
Department of Physiology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, Thailand.

Abstract

The disposition of sulfadoxine was studied in the presence of pyrimethamine in 18 healthy Thai subjects who had been suffering from falciparum malaria in the 6 months prior to the study, and in 12 Thai patients with acute malaria. The volunteers were administered an oral dose of 500 mg sulfadoxine + 25 mg pyrimethamine (1 Fansidar tablet). They were classified retrospectively as responders (Group I, n = 8) or nonresponders (Group II, n = 10) according to previous response to treatment with Fansidar. The patients were treated with 3 Fansidar tablets corresponding to 1500 mg sulfadoxine and 75 mg pyrimethamine. Five of them were completely cured. Seven patients showed R I or R II resistance. In all cases blood samples were collected up to 288 h post dose. The resultant plasma was analyzed for active (i.e. unchanged) and total sulfadoxine using a modified Bratton-Marshall method. In the healthy volunteers the plasma concentration time course of total sulfadoxine was similar for responding and nonresponding subjects. However, in nonresponders active sulfadoxine tended to show shorter half-lives (harmonic means were 212 h vs 267 h, respectively). Furthermore, significantly higher amounts of metabolites (mainly N4-acetylsulfadoxine) were present in plasma of nonresponders. In contrast to these findings, in malaria patients, plasma concentrations of active and total sulfadoxine were even higher in nonresponders as compared to the subjects who could be successfully cured. Furthermore, in this case there was no increase of the amount of metabolites in plasma.(ABSTRACT TRUNCATED AT 250 WORDS).

PMID:
2903623
[Indexed for MEDLINE]

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