The effect of malaria infection on antipyrine metabolite formation in the rat.

We have shown that malaria infection can impair selectively the formation of antipyrine metabolites in the rat. During malaria, a significant increased urinary levels of unchanged antipyrine was observed (control: 1.7 +/- 0.4 vs test: 8.1 +/- 1.1% of dose, P less than 0.001). This was associated with significantly decreased excretion of 3-hydroxymethylantipyrine (control: 24.5 +/- 1.2 vs test: 21.4 +/- 0.7%, P less than 0.001) and 4-hydroxyantipyrine (control: 20.1 +/- 0.9 vs test: 15.5 +/- 1.3%, P less than 0.001) but not norantipyrine compared to control. Following treatment of the malaria infection with halofantrine, only the formation of 3-hydroxymethylantipyrine (control: 25.2 +/- 0.9 vs test: 24.1 +/- 0.6%, P less than 0.05) is impaired. The implications of these findings in relation to metabolism of other antimalarial drugs during malaria remains to be elucidated. Further work is needed to determine the changes in the pharmacokinetics of AP and its metabolites before, during and after MI in the rat in order to give a better insight into the effect of MI on hepatic drug metabolism.