THE PHARMACOKINETIC PROFILE OF RS-8359

RS-8359 is very rapidly absorbed, metabolized and distributed followin g oral dosing, with significant concentrations of both parent drug and its principal metabolite appearing in plasma within 15 min. Plasma le vels were linearly related to doses of up to 300 mg, beyond which abso rption was diminished, perhaps due to a saturation effect. Clearance o f RS-8359 is mainly through the renal system as the metabolite, and is virtually complete within 24 h. The kinetic profile of the drug best fits a two-compartment model, and mean residence time and half-life (b eta) of the drug support a twice a day regimen for extended use. Durin g multiple dosing twice a day for up to 6 weeks, steady state plasma d rug levels were achieved within 48 h and there was no evidence of sign ificant accumulation.