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Date of Award


Document Type

Thesis - Pacific Access Restricted

Degree Name

Master of Science (M.S.)



First Advisor

Timothy J. Smith

First Committee Member

Patrick R. Jones

Second Committee Member

James W. Blankenship


Dapsone has been shown to be an effective agent against Pneumocystis carinii pneumonia, an opportunistic infection in AIDS patients. Oral administration of dapsone is associated with several adverse effects, including methemoglobinemia, hemolytic anemia and photosensitivity reactions. To reduce the adverse effects associated with oral dapsone, an alternative would be to administer the prodrug diacetyldapsone (DADDS) into the lung, which may be hydrolyzed to monoacetyldapsone and the active metabolite dapsone. The purpose of this investigation was to determine the effect of cyclodextrindiacetyldapsone (CD-DADDS) complex upon the cultured lung cells and whether or not cultured lung cells could activate DADDS into dapsone, the active metabolite. The effect of the CD-DADDS complex upon the growth of cultured CRL 7272 lung cells was assessed by the trypan blue dye exclusion technique. There was no significant reduction in cell number as compared to the control for incubations with three different concentrations of CD-DADDS complex. The amount of arylamine produced by hydrolysis was initially monitored by the Bratton-Marshall diazotization technique.

Only incubation with 0.01% DADDS in 1% CD showed a significant time dependent hydrolysis of DADDS over a period of 72 hours due to insensitivity of the assay method. Over the same period, cultured lung cells produced 1.65 μmoles of metabolite/106 cells. However interfering substances could contribute to this value. To provide additional evidence for hydrolysis and to quantitatively estimate the amount of dapsone, a more sensitive HPLC method was used. The results obtained from HPLC analysis demonstrated a significant concentration and time dependent increase in the amount of dapsone with 0.001% DADDS, 0.005% DADDS and 0.01% DADDS incubations, respectively. Over a period of 48 hours, 255ng of dapsone/ 106 cells was formed in an incubation containing 0.01% DADDS.



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