Bioavailability and pharmacokinetics of S-propargyl-L-cysteine, a novel cardioprotective agent, after single and multiple doses in Beagle dogs

Abstract

1. As a novel hydrogen sulfide-modulated agent, S-propargyl-L-cysteine (SPRC) is proven to be a potent cardioprotective candidate. Bioavailability and pharmacokinetics of SPRC (20 mg/kg) in beagle dogs after oral and intravenous administrations were investigated in this study. Plasma concentrations of SPRC were measured by a LC-MS/MS method.

2. Intravenous administration of SPRC (single dose) to beagle dogs gave a mean plasma half-life of 14.7 h, mean clearance of 0.4 ml min⁻¹ kg⁻¹ and mean apparent volume of distribution of 0.56 L/kg. Single oral administration was completely, fast absorbed (T_max= 0.33 ± 0.20 h) with a mean absolute availability of 112% and mean plasma half-life of 16.5 h.

3. Multiple oral administration (once daily for 10 consecutive days) of SPRC to dogs resulted in steady state plasma drug concentration being reached after seven doses and didn’t cause obvious accumulation. No significant difference was found between the single and multiple pharmacokinetic parameters.

Keywords::

• S-propargyl-cysteine
• pharmacokinetics
• bioavailability
• beagle dog