Suramin as a chemosensitizer: oral pharmacokinetics in rats

The purpose of this study was to determine if the 10-50 microM plasma concentrations of suramin required to produce chemosensitization could be achieved by oral administration.

Rats were given an oral dose of 100, 300, or 500 mg/kg unlabeled suramin by oral gavage. Rats receiving the 300 mg/kg oral dose of suramin also received a concomitant intravenous bolus injection of 50 microCi/kg of [3H]suramin, administered 57 min after the oral dose. The intravenous data were used to calculate the clearance. Serial plasma samples were collected over 24-336 h. Plasma concentration-time profiles were analyzed using noncompartmental and compartmental methods. The pharmacokinetic parameters derived for the 300 mg/kg oral and 50 microCi/kg intravenous doses were used to calculate the bioavailability and AUC at the three oral dose levels.

Plasma concentrations declined biexponentially following intravenous administration, with a distribution half-life of approximately 2 h and an estimated terminal half-life of 276 h. Suramin absorption following oral gavage was variable and incomplete with mean maximal plasma concentrations of 9.04, 72.6, and 64.4 microg/ml at doses of 100, 300, and 500 mg/kg, respectively. Seven of 15 rats exhibited two peak plasma concentrations at approximately 1 h and 3 to 12 h, suggesting the existence of multiple absorption sites and/or enterohepatic circulation. Oral bioavailability, calculated using the clearance of the intravenous tracer dose, was <3% at all three dose levels.

While plasma concentrations resulting from the 300 and 500 mg/kg oral doses of suramin were in the concentration range required to produce chemosensitization, the low bioavailability limits the usefulness of oral administration.