Pharmacokinetics of recombinant human basic fibroblast growth factor in rabbits and mice serum and rabbits aqueous humor.
OBJECTIVE
To study the pharmacokinetics of recombinant human basic fibroblast growth factor (rhbFGF) in rabbits and mice after iv and postocular administration, and the changes of rhbFGF in rabbits aqueous humor after postocular administration.


METHODS
After iv or postocular administration three doses of rhbFGF in rabbits and mice, rhbFGF concentration in serum and rabbit aqueous humor was determined by enzyme-linked immunosorbent assay.


RESULTS
Serum concentration-time data of rabbits after iv administration of rhbFGF 1, 2, and 4 micro/kg were fitted to bi-exponential equations with half-lives of 0.9, 0.9, and 0.6 min for T1/2alpha and 7, 8, and 4.7 min for T1/2beta. Plasma concentration-time data of mice after iv administration of rhbFGF 2.5, 5 and 10 microg/kg were fitted to bi-exponential equations with half-lives of 0.4, 0.6, and 0.9 min for T1/2alpha and 6, 5, and 7 min for T1/2beta. The AUCs were linearly correlated to doses in both cases (r rabbit=0.997, r mouse=0.999). The serum concentrations of rhbFGF were very low, near to the background after postocular administration of 2 or 5 microg/kg, in both rabbits and mice. The rhbFGF levels in rabbits aqueous humor were higher than control 8 h postdose (P<0.01).


CONCLUSIONS
rhbFGF within the examined doses had a linear pharmacokinetics in rabbits and mice. High concentration of rhbFGF was found in rabbits aqueous humor after postocular administration.
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Qi
Q
Zhang
Guang-Ji
GJ
Wang
Jian-Guo
JG
Sun
D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D019540:Area Under Curve; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
C100666:KCB-1 protein, recombinant; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2