In 22 lepromatous Filipino patients receiving their first injection of 225 mg
acedapsone (
DADDS),
dapsone (DDS), and monoacetyl DDS (
MADDS) were present in plasma in approximately equal quantities. Peak levels of parent
drug, DDS, and
MADDS occurred between 22 and 35 days. The half-times of disappearance (T1/2) from plasma were 43 days for DDS and
MADDS and 46 days for
DADDS. Acetylator phenotyping with
sulfamethazine (SMZ) and DDS showed that 17 patients were rapid and 5 patients were slow acetylators. Correlations between acetylation of SMZ and DDS after DDS and of acetylation of DDS after DDS and
DADDS were highly significant. However, acetylation of DDS after
DADDS did not differentiate the patients into acetylator phenotypes. The T1/2 of DDS after DDS in the patients was directly related to the minimum levels of DDS at 77 days after
DADDS treatment. These minimum levels were 8-fold higher than the minimum inhibitory concentration (MIC) of DDS for Mycobacterium leprae in mice and rats, but not all patients responded satisfactorily. No relationship could be demonstrated between the bacteriologic response and any of the pharmacologic parameters examined in these Filipino patients. In a companion study, minimum levels of
DADDS,
MADDS, and DDS were determined in 447
leprosy patients of all disease types from the Karimui District of Papua New Guinea who had been receiving 225 mg
DADDS every 70 to 80 days for the past 5 years. All patients exhibited DDS levels above the MIC of DDS for M. leprae, no significant differences in plasma
sulfone levels were found among disease types, no relationship between rate of healing in paucibacillary patients and
sulfone levels were found, and type of response in multibacillary patients and
sulfone levels were unrelated. No substantial accumulation of the
sulfones in the Karimui patients receiving continuous
therapy with
DADDS for 5 years was indicated from a comparison with the levels in the Filipino patients following a single injection of
DADDS.