Dose-ranging study of NG-nitro-L-arginine pharmacokinetics in rats after bolus intravenous administration.
1. NG-nitro-L-arginine (10, 30 and 100 mg/kg) was administered intravenously to the male Wistar rat. Plasma was collected over 48, 72 and 120 h and was analysed for the drug by hplc. Pharmacokinetic parameters were calculated using a non-compartmental method. 2. Drug concentration-time profiles of individual rats after all doses studied exhibited secondary peaks, while geometric mean concentration-time curves showed plateaus. 3. NG-nitro-L-arginine plasma concentrations divided by dose almost coincided. Pharmacokinetic parameters were not dose-dependent in the range of 10-30 mg/kg, but changed after 100 mg/kg of NG-nitro-L-arginine indicating some decline from linearity. 4. NG-nitro-L-arginine is a low-extracted drug in rat as the total clearance was low (0.05-0.07 l/h/kg). Half-life and mean residence time were found to be long (17-30 and 23-40 h, respectively). Despite its low lipophilicity, NG-nitro-L-arginine exhibited large steady-state and terminal volumes of distribution (1.4-2.2 l/kg and 1.4-2.4 l/kg, respectively). Together with the double peak phenomenon, these results may be explained by assuming NG-nitro-L-arginine is involved in a recirculation process in the body.
Institute of Preventive and Clinical Medicine, Bratislava, Slovakia.
V
V
Piotrovskij
Z
Z
Kállay
J
J
Horecký
T
T
Trnovec
G
G
Krumpl
K
K
Krejcy
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008297:Male; D019335:Nitroarginine; D051381:Rats; D017208:Rats, Wistar
D019335:Nitroarginine; D001120:Arginine