Effective administration route for the deleted form of hepatocyte growth factor to exert its pharmacological effects

The pharmacokinetics and the pharmacological effects of the deleted form of hepatocyte growth factor (dHGF) after intravenous (iv), subcutaneous (sc), or intramuscular (im) administration (0.25 and 2.5 mg/kg) were studied in rats. After single iv administration (2.5 mg/kg), dHGF in serum rapidly dec reased (alpha- and beta-phase half-life: 3.2 and 26.5 min, respectively). T wo to four hours after single sc or im administration (2.5 mg/kg), the seru m level of dHGF reached a maximum and then gradually declined (half-life: 2 .7 h). The serum levels were not changed by repetitive iv administration, b ut were dramatically decreased by repetitive sc or im administration. Liver weight and serum levels of total protein, albumin, and HDL-cholesterol wer e significantly increased by iv administration of dHGF (twice daily for 4 d ays at 0.25 mg/kg). Sc or im administration of dHGF did not increase these parameters at the same dose, but did significantly at 2.5 mglkg. These obse rvations suggest that iv administration is the most effective in exerting t he pharmacological effects of dHGF among three administration routes, dHGF after iv administration was distributed mainly and rapidly into liver (53.6 % of the injected dHGF within 5 min) and was sustained at a higher level in the liver than in plasma. In infusion (0.5 mg/kg/3 h), dHGF level in plasm a and liver reached a steady-state 15 and 60 min after starting the infusio n, respectively. The steady-state level of dHGF was 7- to 9-fold higher in liver than in plasma, and the higher level in liver was sustained beyond th e steady-state.