Reassessment of dapsone as a marker of acetylator phenotypes

The ratio of metabolite to parent dapsone concentrations at 3 hours after dosing has been used as a marker of acetylator phenotypes. The absorption of dapsone is somewhat erratic with peak concentrations often found after the 3-hour determination. The present study done in 30 healthy, male volunteers compared ratios of metabolite to parent dapsone concentrations 3 hours after dosing with AUC values calculated during a 24-hour period as well as extrapolated to infinity. A single oral dose of 100 mg of dapsone was given to fasting subjects and serial blood samples were obtained over a 24-hour period and assayed by high-performance liquid chromatography for parent and acetylated metabolite. Dapsone pharmacokinetic parameters of AUC (23.4 +/- 8.6 micrograms.h/ml), half-life (24.8 +/- 11.5 hours) and apparent clearance values (81 +/- 30 ml/min) were consistent with those reported previously. Using established criteria for acetylation phenotyping, 20 percent of the subjects (6 of 30) demonstrated rapid acetylation. Bimodality in the ratios, independent of the experimental indices used to differentiate genetic metabolism, was not readily apparent. The data suggest that large variability in the pharmacokinetics of dapsone may sufficiently obscure the evidence of polymorphic metabolism. The use of dapsone as a marker of acetylator phenotyping should be limited to patient populations.