DISPOSITION OF PROGUANIL IN THAI PATIENTS WITH UNCOMPLICATED FALCIPARUM-MALARIA

The objective of this study was to examine the disposition of proguani l in malaria-infected Thai patients with acute uncomplicated falciparu m malaria, Eleven patients were administered 500 mg of proguanil twice a day for three days (total dose = 3,000 mg). Four patients were tent atively classified as extensive metabolizers (EMs) and seven as poor m etabolizers (PMs). The mean plasma clearances of proguanil for EMs and PMs were 1.31 and 1.10 L/hr/kg, respectively. The mean elimination ha lf-life of proguanil was statistically longer in PMs than EMs (19.6 hr versus 16.1 hr; P = 0.01). Plasma clearance and elimination half-life of proguanil in the malaria patients were comparable with those repor ted in the literature for healthy Thai volunteers, In contrast to othe r ethnic groups, Thai EM patients had relatively low plasma concentrat ions of cycloguanil, the active metabolite of proguanil. None of the 1 1 patients treated with proguanil were cured of malaria and their phen otypic status did not affect the treatment outcome. Although high leve ls of parasite resistance to cycloguanil were probably responsible for the poor response to proguanil treatment, the inability of Thai EM an d PM patients to produce cycloguanil may have also contributed to the treatment outcome.