The disposition of
sulfalene was studied in eight individuals before and during an
infection with a
chloroquine-resistant strain of Plasmodium falciparum.
Isoniazid acetylator phenotype was determined in each individual prior to the administration of
sulfalene. Following the administration of
sulfalene before
infection with
malaria, a significant difference in half-life of non-acetylated
sulfalene and percent acetylation of
sulfalene in plasma was observed between rapid and slow acetylators. When
sulfalene was administered during
malaria, this difference was no longer apparent. Individuals who did not respond to the therapeutic administration of
sulfalene alone were treated with a combination of
sulfalene and
pyrimethamine. Three individuals were cured by
sulfalene without
pyrimethamine and one was cured by the
drug combination. Three of the four individuals who were not cured by any dose of
sulfalene or the
drug combination were slow acetylators. There was no distinct correlation between clinical response and maximum levels or half-life of nonacetylated
sulfalene. These findings suggest that acetylator phenotype does not influence the therapeutic response of individuals infected with
falciparum malaria to
sulfalene or to the combination of
sulfalene and
pyrimethamine. Further information is presented, however, to confirm the importance of an as yet unidentified host factor(s) in determining therapeutic response to these agents.