1993 Volume 8 Issue 6 Pages 1191-1197
We have studied the effect of sialic acid in rG·CSF on the disposition of rG·CSF using monosialo-rG·CSF and disialo-rG·CSF.
1. Monosialo-rG·CSF and disialo-rG·CSF were administered to male rats at the dose of 50μg/kg intravenously and subcutaneously ; plasma and urinary concentrations were measured by EIA.
2. After intravenous administration, the half-lives of α and β phases, Vc, Vss, MRT, CLtotal and CLrenal of monosialo-rG·CSF were 0.24h, 1.07h, 55.25ml/kg, 90.78ml/kg, 1.07 h, 93.30ml/h/kg and 0.004ml/h/kg, respectively. Half-lives of α and β phases, Vc, Vss, MRT, CLtotal and CLrenal of disialo-rG·CSF were 0.27h, 1.17h, 51.84ml/kg, 80.46ml/kg, 1.24h, 61.56ml/h/kg and 0.026ml/h/kg, respectively. The CLtotal of monosialo-rG·CSF was significantly greater than that of disialo-rG·CSF.
3. After subcutaneous administration, the Tmax of monosialo-rG·CSF was 1.75h and was shorter than 3.5h of disialo-rG·CSF. Cmax, apparent half-life, MRT, AUC, CLrenal, MAT and F for monosialo-rG·CSF were 54.01ng/ml, 2.06h, 3.99h, 302.18ng·h/ml, 0.003ml/h/kg, 3.08h and 0.56, respectively. The Cmax, apparent half-life, MRT, AUC, CLrenal, MAT and F for disialo-rG·CSF were 57.84ng/ml, 2.37h, 5.31h, 396.92ng·h/ml, 0.030ml/h/kg, 4.07h and 0.49, respectively. The AUC and MRT of disialo-rG·CSF were significantly greater than those of monosialo-rG·CSF.
4. There were some differences in dispositions between monosialo-rG·CSF and disialo-rG ·CSF. These results have suggested that sialic acids in rG·CSF molecule modify the elimination and absorption of rG·CSF.
