LACK OF EFFECT OF PROGUANIL ON THE PHARMACOKINETICS OF DAPSONE IN HEALTHY-VOLUNTEERS

The multiple-dose kinetics of dapsone (DDS) and its principal metaboli te monoacetyldapsone (MADDS) were determined in 6 healthy volunteers a fter daily administration of low-dose dapsone (10 mg). Comparison with a previous study involving the same volunteers on a daily regimen of proguanil (200 mg) plus dapsone (10 mg) revealed no statistically sign ificant differences in the maximum plasma concentrations, area under t he plasma drug concentration curves and elimination half-lives of both DDS and MADDS in the presence of proguanil. Although these findings s uggest that proguanil does not alter the pharmacokinetics of DDS and M ADDS, the possibility that proguanil affects the disposition of hydrox ylated metabolites of dapsone, which appear to mediate dapsone toxicit y, cannot be excluded.