Sensitivity to Glucantime (R) of Leishmania viannia isolated from patientsprior to treatment

In vitro sensitivity to pentavalent antimony (SbV) as meglumine antimoniate (Glucantime(R)) of Leishmania of the Viannia subgenus isolated Drier to tr eatment from patients with uncomplicated cutaneous leishmaniasis was evalua ted fur intracellular amastigotes in the U-937 human monocytic cell line an d log phase promastigotes. The 50% effective dose (ED50) of pharmaceutical and additive-free formulations of Glucantime were determined based on the k inetics of the response of Leishmania Viannia to SbV in vitro. ED50 to SbV was inversely related to time of exposure to drug. The potency of the addit ive-free formulation of Glucantime was significantly greater than that of t he pharmaceutical formulation, irrespective of the parasite form. In vitro sensitivity to SbV ranged from <5.3 mu g/ml to >170.0 mu g/ml Under the con ditions used, 11 (39%) of 28 strains were sensitive to clinically achievabl e serum concentrations of SbV. No correlation was observed between the tota l amount of SbV required for healing of lesions and the in vitro response t o the pharmaceutical formulation of Glucantime. In contrast, a significant correlation (P = 0.001) was observed between clinical response and the in v itro sensitivity of promastigotes to the additive-free formulation of Gluca ntime. The greater potency of the additive-free formulation of Glucantime, the correlation of in vitro sensitivity of promastigotes to this formulatio n and the clinical response to treatment, and the effect of time of exposur e to SbV demonstrate the importance of assay conditions on the outcome and interpretation of in vitro evaluation of drug sensitivity.