Influence of acetylator phenotype of the leprosy patient on the emergence of dapsone resistant leprosy.

The half time of disappearance of dapsone and monoacetyl dapsone and the acetylator phenotype of the leprosy patients who harboured dapsone sensitive and dapsone resistant M. leprae was assessed in 27 subjects. Sixteen patients were rapid acetylators, five were slow and six were intermediate acetylators. The mean T 1 1/2 lives of dapsone (30.26 +/- 11.0) and monoacetyl dapsone (31.11 +/- 12.0) were also studied in the above patients. The percentage of different acetylators in both resistant and sensitive groups were similar showing no correlation between the emergence of drug resistance and the phenotype of the patient. The mean time of disappearance of DDS and MAD in the different acetylators did not show significant difference. The ratios of MAD/DDS in an individual at 3, 6 or 24 hours after the dose were similar. The mean T 1 1/2 lives of DDS and MAD in resistant and sensitive patients also showed no difference. Neither T 1 1/2 lives of DDS or MAD nor the acetylator phenotype seem to influence the emergence of dapsone resistance.

Blood dapsone levels in leprosy patients treated with acedapsone.

The metabolism of the repository drug acedapsone (DADDS,4,4'-diacetyldiaminodiphenyl sulfone) was studied in 15 individuals receiving 225 mg of DADDS, intramuscularly for a period of 75 days. Plasma levels of DDS were determined on the 2nd, 7th, 15th, 30th, 60th and 75th day after administration of the drug by spectrophoto-fluorometric technique. The mean peak levels of DDS (85.36 ng/ml) were noticed on 7th day followed by a gradual decrease in DDS concentration. The mean half-life level (44.53 ng/ml) of DDS were observed around the 15th day. The mean DDS level for the entire period of observation after one dose was 41.95 ng/ml. On the 75th day, the DDS level reached the minimum value of 14.76 ng/ml which was still about 5 times more than the minimal inhibitory concentration (MIC) level of DDS against M. leprae (3 ng/ml). The results are discussed.

Limited duration acedapsone prophylaxis in leprosy.

A randomized controlled chemoprophylaxis trial was carried out in Madras city using 560 disease-free household child contacts of 264 multibacillary cases as study subjects. In the study, 13 cases were diagnosed among 280 contacts who received 3 injections of acedapsone at 10 weeks interval as against 30 cases among 280 contacts who had the same number of placebo injections, during the follow-up period of 225 weeks. The difference in the incidences in the two groups was statistically significant. (X2 6.45; P less than 0.02). The protection due to the limited duration of acedapsone prophylaxis was 56.7 percent. There were no cases of multi-bacillary leprosy in either group. The efficacy of prophylaxis was significant in male children over 9 years of age and female children in the age-group 1-8 years. The other prognostic factors like the infectivity status of the index cases in the household and the duration of exposure to them could have possibly influenced the effectiveness of prophylaxis in preventing progression from infection to clinical disease among the subjects studied. Their effects could not be assessed in this study.

Armadillo as a model for studying chemotherapy of leprosy: preliminary studies.

In order to determine the suitability of the armadillos as a model of human leprosy for chemotherapeutic studies, especially in evaluating newer anti-leprosy drugs, uninfected Armadillos were used to study the metabolic disposition of DDS. Serum DDS levels ranged from 500 ng/ml at 3 hours to 13 ng/ml at 96 hours after intravenous administration of DDS (1 mg/kg). In an ad libitum feeding trial of DDS it was found that the level of serum DDS varied according to the dose of DDS, and even at a dose of 0.0001%, the animals maintained MIC of DDS against M. leprae. Finally, it was demonstrated that armadillos acetylate DDS to MADDS and 7-9% of DDS is acetylated by armadillos.