V. Piotrovskij et al., DOSE-RANGING STUDY OF N-G-NITRO-L-ARGININE PHARMACOKINETICS IN RATS AFTER BOLUS INTRAVENOUS ADMINISTRATION, Xenobiotica, 24(7), 1994, pp. 663-669
1. N-G-nitro-L-arginine (10, 30 and 100 mg/kg) was administered intrav
enously to the male Wistar rat. Plasma was collected over 48, 72 and 1
20h and was analysed for the drug by hplc. Pharmacokinetic parameters
were calculated using a non-compartmental method. 2. Drug concentratio
n-time profiles of individual rats after all doses studied exhibited s
econdary peaks, while geometric mean concentration-time curves showed
plateaus. 3. N-G-nitro-L-arginine plasma concentrations divided by dos
e almost coincided. Pharmacokinetic parameters were not dose-dependent
in the range of 10-30 mg/kg, but changed after 100 mg/kg of N-G-nitro
-L-arginine indicating some decline from linearity. 4. N-G-nitro-L-arg
inine is a low-extracted drug in rat as the total clearance was low (0
.05-0.071/h/kg). Half-life and mean residence time were found to be lo
ng (17-30 and 23-40h, respectively). Despite its low lipophilicity, N-
G-nitro-L-arginine exhibited large steady-state and terminal volumes o
f distribution (1.4-2.21/kg and 1.4-2.41/kg, respectively). Together w
ith the double peak phenomenon, these results may be explained by assu
ming N-G-nitro-L-arginine is involved in a recirculation process in th
e body.