Hydralazine-induced lupus: is there a toxic metabolic pathway?

The metabolism of hydralazine in a group of slow acetylator patients with the drug-induced lupus syndrome was compared with the metabolism in asymptomatic control subjects. There were no toxicologically significant difference in metabolite excretion between the groups which reached statistical significance, although there were interesting trends. However, the single lupus patient with the rapid acetylator phenotype excreted considerably greater quantities of phthalazinone than control patients and also increased amounts of hydrazine and hydralazine hydrazones. These results and the trends overall are consistent with the hypothesis that the metabolism of hydralazine may indeed be responsible for the drug induced lupus syndrome.