PMID- 9874714
OWN - NLM
STAT- MEDLINE
DCOM- 19990322
LR  - 20131121
IS  - 0022-3549 (Print)
IS  - 0022-3549 (Linking)
VI  - 88
IP  - 1
DP  - 1999 Jan
TI  - Effective administration route for the deleted form of hepatocyte growth factor 
      To exert its pharmacological effects.
PG  - 131-5
AB  - 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 decreased 
      (alpha- and beta-phase half-life: 3.2 and 26.5 min, respectively). Two to four 
      hours after single sc or im administration (2.5 mg/kg), the serum 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, but were dramatically 
      decreased by repetitive sc or im administration. Liver weight and serum levels of 
      total protein, albumin, and HDL-cholesterol were significantly increased by iv 
      administration of dHGF (twice daily for 4 days 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 mg/kg. These observations suggest that iv administration 
      is the most effective in exerting the 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 plasma and liver reached a steady-state 15 and 60 min after starting the 
      infusion, 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 the 
      steady-state.
FAU - Uematsu, Y
AU  - Uematsu Y
AD  - Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., 519 
      Shimoishibashi, Ishibashi-machi, Shimotsuga-gun, Tochigi 329-0512, 
      Japan.snowls0@mb.infoweb.ne.jp
FAU - Fujise, N
AU  - Fujise N
FAU - Kohsaka, K
AU  - Kohsaka K
FAU - Masunaga, H
AU  - Masunaga H
FAU - Higashio, K
AU  - Higashio K
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Immunoglobulin G)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.11.1.7 (Peroxidase)
SB  - IM
MH  - Animals
MH  - Cholesterol/blood
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Half-Life
MH  - Hepatocyte Growth Factor/*administration & dosage/immunology/*pharmacology
MH  - Immunoglobulin G/immunology
MH  - Injections, Intramuscular
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Liver/cytology/drug effects/physiology
MH  - Liver Function Tests
MH  - Male
MH  - Organ Size/drug effects
MH  - Peroxidase/chemistry
MH  - Rabbits
MH  - Rats
MH  - Rats, Wistar
EDAT- 1999/01/06 06:49
MHDA- 2000/07/19 11:00
CRDT- 1999/01/06 06:49
PHST- 1999/01/06 06:49 [pubmed]
PHST- 2000/07/19 11:00 [medline]
PHST- 1999/01/06 06:49 [entrez]
AID - S0022-3549(15)50750-8 [pii]
AID - 10.1021/js9800432 [doi]
PST - ppublish
SO  - J Pharm Sci. 1999 Jan;88(1):131-5. doi: 10.1021/js9800432.