Is recombinant human granulocyte colony-stimulating factor (G-CSF) orally available in rats?
Oral availability of recombinant human granulocyte colony-stimulating factor (G-CSF) was investigated in rats by measuring the blood total leucocyte (BTL) counts. Oral test G-CSF solution was prepared with 10% HCO-60 (polyoxyethylated, 60 mumol, castor oil derivative), 1% DK ester (sugar ester) or 10% MYS-40 (polyethyleneglycol monostearate), in which the G-CSF concentration was 500 or 250 micrograms/ml. Each test solution was injected into the duodenum of three rats at the G-CSF dose level of 300 or 600 micrograms/kg, and BTL counts were monitored for 48 h. All of the test G-CSF solution raised the BTL levels within 24 h after injection. In particular, the HCO-60 solution increased the BTL levels over 2 times as compared to the predose level at 600 micrograms/kg dose and the effect was apparently dose-dependent. A short-term study suggested that the effect of G-CSF on the BTL level appeared at the fastest at about 5 h after administration of HCO-60 test solution, 300 micrograms/kg. In view of the pattern of BTL dynamics obtained after i.v. injection of HCO-60 solution at 25 and 50 micrograms/kg, the increase of BTL levels observed after oral administration of the HCO-60 solution is considered to be due to the orally supplied G-CSF.
Takada
K
K
Tohyama
Y
Y
Oohashi
M
M
Yoshikawa
H
H
Muranishi
S
S
Shimosaka
A
A
Kaneko
T
T
D000818:Animals; D001682:Biological Availability; D003115:Colony-Stimulating Factors / Q000096:biosynthesis / Q000493:pharmacokinetics*; D016179:Granulocyte Colony-Stimulating Factor; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000493:pharmacokinetics
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor