Drugs 45 (Suppl. 3): 225-226, 1993 0012-666 7/93/0300-0225/$1.00/0 © Adis International Limned. All rights reserved. DRSUP5516q Clinical Trial of Sparfloxacin in the Treatment of Leprosy Scott G, Franzblau l and Gertrude p, Chan 2 I GWL Hansen's Disease Laboratory Research Branch, Baton Rouge, Louisiana, USA 2 Research Institute for Tropical Medicine, Metro Manila, Philippines The recent development of radiorespirometric assays for rapidly assessing the viability and drug susceptibility of Mycobacterium leprae in vitro has facilitated the identification of new potential an- tileprosy drugs (Franzblau et aL 1992), A compar- ative radiorespirometric study of 20 fluoroquino- lones found sparfloxacin (AT-4140) to be the most active quinolone, with in vitro activity surpassing that of both pefloxacin and ofloxacin (Franzblau & White 1990). A comparative study (vs ofloxacin) in nude mice confirmed the in vitro observations. Considering its favourable plasma half-life (16 hours) and efficacy in other intracellular infections, sparfloxacin was selected for clinical trial in patients with leprosy. Sparfloxacin 200mg daily was chosen for comparison with an earlier trial of ofloxacin 400mg (Grosset et aL 1990). In addition to clinical response and mouse foot- pad infectivity, patient response was monitored by measurement of serum phenolic glycolipid-I (PGL- I) antigen and radiorespirometric activity of serial biopsy-derived M. leprae. Nine previously untreated patients with a bac- terial index of at least 4+, morphologic index of at least I + and at least I site suitable for the taking of 5 biopsies were recruited. Patients, who were confined at the Research Institute for Tropical Medicine for the initial 8 weeks of the study, re- ceived the following regimen: day I, 400mg load- ing dose; days 2 to 56, 200mg daily; and days 57 to 84, 200mg daily (outpatient). Six millimetre skin punch biopsies, serum and urine were collected just before initiation of treat- ment and at 2-week intervals thereafter for 8 weeks. Patients were observed weekly. Clinical response was graded on the basis of erythema, diffuse infil- tration, size/elevation of nodules and plaques. For determination of serum PGL-I, sera were dried, and lipids were extracted and then fraction- ated on florisil columns. PGL-I was detected by reaction with rabbit antiPGL-I antiserum and per- oxidase-conjugated goat antirabbit, using 4-chloro- I-napthol as substrate. Groups of 10 mice were inoculated with 5000 biopsy-derived M. /eprae. For pretreatment biop- sies, additional groups of 10 mice were inoculated with 500, 50 and 5 acid-fast bacilli (AFB). 10 6 biopsy-derived M. leprae were added to 7HI2 medium + I /-LCi [1-14C]palmitic acid. An equivalent number of heat-killed AFB were added to replicate vials to serve as controls. Evolution of labelled carbon dioxide was determined as previ- ously described (Franzblau et aL 1992) after I week's incubation at 33°C. Patients receiving sparfloxacin showed im- provement in the appearance of their lesions after only 2 weeks' treatment. At 4 weeks of treatment, clinical improvement was approximately 50%, in- creasing to 70 to 95% by 8 to 12 weeks of treat- ment. There was a concurrent decline in PGL-I antigen during treatment. Eight of 9 patients had a 3+ titre before treatment and half of these were rated ± at the end of8 weeks' treatment. No patient had a titre of > I + after 12 weeks of treatment. Bacilli taken from the 2-week post-treatment biop- sies showed a reduction in radiorespirometric ac- tivity of 75 to 99% compared with pretreatment activity. After 4 weeks of treatment, there was no detectable radiorespirometric activity, suggesting rapid bactericidal activity of sparfloxacin. Spar- floxacin was well tolerated, with only minor side effects noted during the first week. Mild reversal reaction was noted in I patient. Subsequent harvesting of mouse footpads will allow for correlations to be made between the newer rapid methodologies and the traditional mouse footpad assay. The results of this study are sum- marised in table I; overall, these suggest ihat spar- floxacin 200mg may give results comparable to those found previously with ofloxacin 400mg. Fur- ther studies are warranted to determine the quin- olone of choice for leprosy. Table I. Summary of results Sparfloxacin effected a rapid clinical response in patients with leprosy Radiorespirometric activity was undetectable after 4 weeks of treatment Serum phenolic glycolipid-I antigen declined during treatment in all patients Results with sparfloxacin 200mg appear comparable to those obtained in a previous trial of ofloxacin 400mg