Clinically relevant suramin dosing regimen in mice with no effects against PC-3 prostate xenografts

The goal of these studies was to develop a suramin dosing schedule that would maintain suramin plasma concentrations in mice in the 150-250 mu g/ml range. A high pressure liquid chromatography method was used to determine suramin plasma concentrations in mice. For pharmacokinetic studies CD2F(1) mice were treated intraperitoneally with 140 mg/kg of suramin. These pharmacokinetic data were used to develop a clinically relevant dosing regimen. To test the efficacy of this dosing regimen, athymic nude mice were implanted orthotopically with PC-3 prostate carcinoma cells, randomized, and treated intraperitoneally. The pharmacokinetically derived dosing regimen resulted in no antitumor effect against PC-3 prostate tumors. Suramin plasma concentrations ranged from 155 to 258 mu g/ml over the 14-day therapy period with tumor concentrations in the 53-241 mu g/g wet weight range.