Pharmacokinetics, plasma protein binding and urinary excretion of N omega-nitro-L-arginine in rats

The in vivo disposition of N omega-nitro-L-arginine (L-NOARG) has been examined in rats. Plasma concentrations of L-NOARG following an intravenous dose of 10 mg kg-1 were determined by high-performance liquid chromatography. Plasma L-NOARG concentrations declined biexponentially, with average half-lives of 11 min and 20 h. L-NOARG clearance did not appear to exhibit concentration-dependency below a plasma concentration of 4.56 x 10(-4) M (100 mg l-1). Ultrafiltration studies revealed insignificant binding of L-NOARG to rat plasma proteins. Urinary excretion of unchanged L-NOARG was minimal. These pharmacokinetic information may be useful in the design of in vivo experiments involving L-NOARG, as well as in the interpretation of the pharmacodynamics of this important nitric oxide synthase inhibitor.