Pharmacokinetics of intravenous and oral L-arginine in normal volunteers

Aims Recent studies in patients with cardiovascular diseases suggest potential for the use of orally administered L-arginine, the precursor of nitric oxide, as a therapeutic agent. This crossover study was designed to examine the pharmacokinetics of single i.v. and oral doses of L-arginine in healthy volunteers (n = 10). Methods A preliminary control study (n=12) was performed to assess the variation in plasma L-arginine concentrations when ingesting a normal diet. The observed variation was taken into account when interpreting the pharmacokinetic data obtained after exogenous administration. Results The mean baseline plasma concentration of L-arginine in the control study was 15.1 +/- 2.6 mu g ml(-1) After intravenous administration (30 g over 30 min), the plasma concentration reached 1390 +/- 596 mu g ml(-1). The disappearance of L-arginine appeared biphasic, with an initial rapid disappearance due to concentration-dependent renal clearance followed by a slower fall in plasma concentrations due to nonrenal elimination. The peak concentration after oral administration (10 g) was 50.0 +/- 13.4 mu g ml(-1), occurring 1 h after administration. Renal elimination was not observed after oral administration of this dose. The absolute bioavailability of a single oral 10 g dose of L-arginine is approximate to 20%. Conclusions This study provides basic knowledge of L-arginine pharmacokinetics in healthy humans. Intravenous and oral administrations show at minimum a biphasic pattern. Further studies will assess whether a similar profile is observed when the drug is administered to patients.