PHARMACOKINETICS OF ANTIMONY IN PATIENTS TREATED WITH SODIUM STIBOGLUCONATE FOR CUTANEOUS LEISHMANIASIS

The pharmacokinetics of Sb was examined in 29 patients with cutaneous leishmaniasis following the intramuscular administration of a dose of sodium stibogluconate equivalent to 600 mg of Sb. Blood was sampled at different time intervals from each patient and Sb was measured in who le blood by electrothermal atomic absorption spectrophotometry after a n appropriate dilution with Triton X-100. The 24-hr urine was also col lected and analyzed similarly. The blood concentration-time data confo rmed to the one-compartment open model with mean and (SEM) of the appa rent first-order rate constants for absorption (k(a)) and elimination (k(d)) of 1.71 (0.15) and 0.391 (0.016) hr(-1), respectively. The maxi mum concentration of Sb achieved was 8.77 (0.39) mg/L and the peak tim e was 1.34 (0.09) hr. The total body clearance (TBC) and the volume of distribution (V-d) were 17.67 (1.38) L/hr and 45.7 (2.6) L, respectiv ely, assuming a complete absorption. The fraction of dose of Sb excret ed in the urine was 0.80 (0.07) and the renal clearance was 12.7 (1.16 ) L/hr. The frequency distribution pattern of the area-under-the-curve (AUC) appears to be bimodal and separates patients into those with lo w exposure to Sb (AUC = 11.7-29.04 mg.hr/L) (i.e., rapid eliminators) and those with high exposure to Sb(AUC = 31.5-49.1 mg.hr/L) (i.e., slo w eliminators). This may explain the variability observed in the respo nse to treatment of leishmaniasis with sodium stibogluconate.