The Study Of Pharmacokinetics Of Recombine Human Endostatin And Its Process Within Body

OBJECTIVES: To study the pharmacokinetics, distribution and the excretion of recombine human Endostatin in rats and mice for a safe and rational individualized dosage regimen. METHODS: Twenty eight rats were randomly divided into four groups of ih rhEndostatin 3. 4mg/kg (9. 35×106cpm/kg), 6. 8mg/kg (9. 42 × 106cpm/kg), 13. 6mg/kg(3. 46 × 107cpm/kg) and iv 3. 4mg/kg (0. 66 × 107cpm/kg), respectively. The radioactivity of blood was determined after administration. Other four rats were i.h or i.v administered respectively. The radioactivity of 125I-Endostantin and the total radioactivity of samples were compared at different sampling time points via SDS-PAGE electrophoresis and then the pharmacokinetic parameters were calculated. Forty mice were divided into five groups at random for i. h administration. At five different sampling time points after administration, the mice were sacrificed, and the heart, liver, lungs, spleen, kidneys, large intestine, small intestine, brain, muscles and blood were excised and weighted, also the radioactivity of each tissue was determined. Bile samples collected from eight bile ducts cannulated rats andtheir radioactivity was determined which showed the cumulative radioactivity elimination time courses of bile duct. After i. h administered, urine and manure samples were collected from ten mice at six different sampling time points, and the radioactivity of each sample was determined. RESULTS: Pharmacokinetic parameters of Endostatin from rats were showed as table 9-15, from which we can get the results as follows: t1BI and Ciai of ih administration are: 0. 55h, 10. 2u g/mg(high dose group), 0. 65h, 4. 85 n g/mg(middle dose group) and 0. 81h, 3. 22 y g/mg (low dose group), shows that Cmi is related with dose. However, ti/2P is 6. 46hs(high dose group), 8. 61hs (middle dose group) and 10. 83hs (low dose group). ti/2P of i. h administrated rat is 6. 5 times as long as of iv administrated. Corresponding to t,/20 , MRT is 11. Ohs, 17. 9hs and 15. 7hs respectively and MRT in low dose group of i. h administrated rat is 6. 8 times as long as of iv administrated. Tissue distribution in mice: Tissue distribution at different sampling time points after i.h administrated of mice is showed as table 1-5 and figure 1-5, from which we can get the peak value of various tissues as follows: kidney(45. 6)> small intestine(11. 8)> liver(10. 9)> lungs (8. 6) > large intestine (7. 8) > spleen(6. 7) > muscles (4. 8) > heart(4. 8)> brain(1.1). The data above shows that Endostatin...