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Biomedical subjects

G C Scott

Publications and source records attributed to G C Scott.

At least 55 records · Page 3Linked to original sources

Acedapsone treatment of leprosy patients: response versus drug disposition.

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.

Acedapsone↗

Acedapsone (DADDS) treatment of leprosy patients in the Karimui of Papua New Guinea: status at six years.

Acedapsone (DADDS), a repository sulfone given by injection five times a year, has been used since 1967 for the treatment of all leprosy patients in the Karimui, an area of diffic-lt access. More than 460 patients have been treated, 336 beginning in November 1967 and continuing through the latest assessment 6 years later. The injections have been well received and they have been administered very regularly. Clinical observations were begun before 1967, as a base-line of assessments was available for the patients whose disease appeared before that time. The response to DADDS therapy has been satisfactory except in 5 of the 28 multibacillary patients in whose smears solid-staining Mycobacterium leprae have reappeared. M. leprae was isolated in mice from three of these patients; one strain has been proven to be completely susceptible to dapsone (DDS), and the other two very probably are. DDS levels in the plasma of these five patients were normal and well above the minimal inhibitory concentration. The most probable explanation is that a few viable M. leprae survived in the presence of inhibitory concentrations of DDS for the 4 to 6 years during which dead bacilli were disintegrating and disappearing from the tissues. The other 23 multibacillary patients responded satisfactorily. The decrease in the number of M. leprae in the skin smears has been most prompt in patients with low initial bacterial loads and in those with borderline lepromatous diagnoses. A high initial bacterial load and a fully lepromatous diagnosis were associated with a slow initial loss of M. leprae in the 1st year, followed by a more rapid loss the next year. All of the multibacillary patients have now been treated by the addition of a 90-day course of rifampicin.

Acetamides↗