Intra-adipose administration of monoacetyldapsone to healthy volunteers.

ABSTRACT

The pharmacokinetics of intra-adiposely administered monoacetyldapsone (particle size less than 20 micron) were investigated in 11 male and 11 female healthy volunteers. Dapsone and monoacetyldapsone concentrations in serum were determined by high-pressure liquid chromatography (HPLC). Injection of 1175 mg monoacetyldapsone, which is equivalent to 1000 mg dapsone, resulted in dapsone concentration/time profiles in all the volunteers characterized by peak concentrations ranging from 0.14 to 0.85 mg/l, and by averaged dapsone concentrations after 28, 42, and 56 days of 0.33, 0.19, and 0.10 mg/l, respectively. Areas under the curves ranged from 6.7 to 25.3 mg X day/l. Detectable concentrations (greater than 6 ng/ml) of dapsone were achieved for 56 days in most of the subjects. An estimation of the mean concentration after repeated injection every 4 weeks ranged from 0.24 to 0.90 mg/l. No differences in dapsone concentration/time course were detectable between men and women or between rapid and slow acetylators. The injection was generally well tolerated by the subjects. This, combined with the excellent sustained release properties, makes it a promising injection. In the future, it might contribute to combat noncompliance among leprosy patients, which is believed to be one of the main causes of dapsone resistance.