Aims Recent studies in patients with cardiovascular diseases suggest potent
ial 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 health
y volunteers (n = 10).
Methods A preliminary control study (n=12) was performed to assess the vari
ation in plasma L-arginine concentrations when ingesting a normal diet. The
observed variation was taken into account when interpreting the pharmacoki
netic 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). Th
e disappearance of L-arginine appeared biphasic, with an initial rapid disa
ppearance due to concentration-dependent renal clearance followed by a slow
er fall in plasma concentrations due to nonrenal elimination. The peak conc
entration after oral administration (10 g) was 50.0 +/- 13.4 mu g ml(-1), o
ccurring 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 pharmacokinet
ics 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.