Application of Spectrophotofluorometric Procedures to Some Problems in Mycobacterium Leprae Infections in Mice and Man Treated with Dapsone (DDS), Diacetyl-DDS (DADDS), and Di-Formyl-DDS (DFD)

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  • Leprosy and Rickettsial Diseases Unit, Virology Section, Center for Disease Control, U.S. Public Health Service, Health Services and Mental Health Administration, The Schieffelin Leprosy Research Sanatorium, Atlanta, Georgia 30333

Recently described spectrophotofluorometric procedures for the determination of dapsone (DDS), which are sensitive to about 10 ng per ml blood or plasma, were applied to several problems in experimental and natural infections with Mycobacterium leprae. Measurements on blood of mice receiving minimal effective dosages showed that the minimal inhibitory concentration of DDS for M. leprae is in the range 2.5 to 10 ng per ml. In mice that had received DDS by mouth, DDS was rapidly eliminated from the blood with a half-life of 3 to 5 hours or less; thereafter a presumed metabolite of DDS was eliminated with a half-life of 6 to 10 days. A procedure was developed for the determination of di-formyl DDS (DFD) in the presence of DDS; measurements on the blood of mice receiving DFD by mouth indicated that the DFD was nearly completely converted to DDS. In patients receiving repository injections of DADDS (di-acetyl DDS), the blood levels averaged 50 ng per ml, or about what would be expected for the absorption of 2.4 mg DDS per day; no blood levels below the minimal inhibitory concentration were encountered. In patients receiving 5 or 10 mg DDS per day orally, some unexpectedly low serum levels of DDS were found.

Author Notes

Present address: National Institute for Leprosy Research, Tokyo, Japan.