Renal failure was experimentally induced in 36 hamsters by
intraperitoneal injection with
uranyl nitrate (5 mg/kg). Twenty-four h later [during
acute renal failure (ARF), as indicated by the serum concentrations of
creatinine and
urea nitrogen] or 72 h later [during
chronic renal failure (CRF)] these hamsters plus 18, uninjected, control hamsters were each given a single, intramuscular dose of
sodium stibogluconate (120 mg pentavalent
antimony/kg). The pharmacokinetic parameters for the antimonial
drug were calculated using a non-compartmental model. Urine was collected for 72 h after similar treatment with the antimonial
drug, from another 30 hamsters (10 controls, 10 with ARF, and 10 with CRF), so that the fraction of the
antimony administered that was subsequently excreted in the urine could be estimated. Compared with the controls, both the hamsters with ARF and those with CRF had significantly higher maximum concentrations of
antimony (C(max)), significantly larger 'areas under the curve' for the plots of blood concentration v. time, and significantly longer plasma half-lives (P < 0.001 for each). The mean (S.D.) values of C(max), for example, were more than three-fold higher in the hamsters with ARF [467.5 (59.04) microg/ml] or CRF [461.1 (68.9) microg/ml] than in the controls [154.01 (17.3) microg/ml]. The systemic clearance of
antimony was also significantly lower in the hamsters with CRF than in the control animals [0.051 (0.002) v. 0.296 (0.047) litres/h/kg; P < 0.01]. In addition, the fraction of the
antimony administered that was excreted in urine was significantly lower in the animals with ARF (0.25) or CRF (0.08) than in the controls (0.37), indicating significant dysfunction of the kidneys in the hamsters injected with
uranyl nitrate. It seems clear that, if severe toxicity is to be avoided, patients with renal dysfunction requiring treatment (for
leishmaniasis) with
sodium stibogluconate should be given lower doses than similar cases with normal kidney function.