OXIDATIVE ACTIVATION OF PROGUANIL AND DAPSONE ACETYLATION IN THAI SOLDIERS

The prevalence of putative poor metaboliser (PM) phenotypes of proguan il oxidation in Caucasian populations is 3-10%. The PM frequency in Or iental populations is unknown. In this study the plasma metabolic rati os of proguanil and dapsone to their principal metabolites cycloguanil and monoacetyldapsone were determined in Thai soldiers receiving anti folate drug combinations for malaria prophylaxis. The distribution rat io of proguanil to cycloguanil (PROG/CYC) was highly skewed with no ev idence of bimodality. Assuming subjects with a PROG/CYC ratio greater than 10 are PMs from studies in Caucasians, the incidence of PMs in th e soldiers would be 18% (30 of 170). The mean PROG/CYC ratio for PMs i n the Thai soldiers was 31.2 +/- 28.9 (n = 30) compared with 25.5 +/- 2.5 (n = 3) in a study of Caucasians. The corresponding values for put ative EMs were 5.4 +/- 2.1 (n = 140) and 2.4 +/- 0.2 (n = 134). Simila r to other Oriental populations, Thais were found to be predominantly (76%, 173 of 228) rapid acetylators of dapsone.