Pharmacokinetics of (Me)Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt and (Me)Arg-Lys-Pro-Trp-tert-Leu-Leu administered intravenously to beagle dogs.

The pharmacokinetics of two analogues (NT-1 and NT-2) of the smallest active fragment of neurotensin were investigated in beagle dogs after intravenous (iv) administration at the doses of 0.1 and 0.5 mg/kg for NT-1 and of 0.25 and 0.5 mg/kg for NT-2. After iv administration of these two drugs, the plasma levels decreased with time with a biexponential pattern, and linear kinetic behavior was observed. The pharmacokinetic parameters (mean +/- standard error of mean) after iv administration of NT-1 at 0.1 mg/kg were as follows: the half-life of the distribution phase (t1/2 alpha) was 0.29 +/- 0.11 h, the half-life of the terminal phase (t1/2 beta) was 1.99 +/- 0.41 h, total plasma clearance (CL) was 33.2 +/- 6.3 mL/h/kg, steady-state volume of distribution (Vdss) was 57.1 +/- 2.8 mL/kg, and mean residence time (MRT) was 2.20 +/- 0.55 h. The t1/2 alpha, t1/2 beta, CL, Vdss, and MRT values after iv administration of NT-2 at 0.25 mg/kg were 0.11 +/- 0.02 h, 0.58 +/- 0.04 h, 257.3 +/- 17.2 mL/h/kg, 180.3 +/- 4.6 mL/kg, and 0.71 +/- 0.04 h, respectively. After iv administration of NT-1, NT-2 was detected in the plasma. It was confirmed from this result that NT-1 was metabolically hydrolyzed to NT-2 in the body of beagle dog.