The Intestinal Absorption Mechanism Of Guanfu I And Its Stability In Different PH

Objective: The absorption mechanism and stability of Guanfu base I(GFI) were investigated through an in site single-pass intestinal perfusion model, and a vitro incubation model, respectively.Methods:The in site rat single-pass intestinal perfusion model was used to investigate the intestinal absorption sit and mechanism of GFI, the influence of different factors(perfusion process speed, the concentration of the perfusion fluid, bowel perfusion, perfusion added with p-gp in hibitors verapamil and application sexes mice) on its absorption efficiency was also evaluated. The concentration of GFI in perfusate was detected by LC-MS, and calibrate the error through the gravimetric method.The stability of GFI in different p H(37℃)was investigated through incubating in fluids, extracting with diethyl ether, drying, and then reconstituting for injection.Result:The Ka of different concentrations(1, 4 and 8μg/m L) of GFI were 0.210±0.032, 0.219±0.019 and 0.205±0.053 h-1, there is no significant differences among them; the Ka of different perfusion rate(0.2,0.4and0.8ml/min) were 0.234±0.018, 0.206±0.034 and 0.237±0.028 h-1,with the increase of the speed of the perfusate, the constant rate of drug absorption was reduced, and there was a significant difference; the Ka of different p H(6.8, 7.4 and 8.0) were 0.221±0.102, 0.235±0.129 and 0.205±0.093 h-1, there was no difference between p H 6.8 and 7.4, but there was a significant among 6.8, 7.4 and 8.0. the Ka of different intestinal segments( duodenum, jejunum, ileum, colon) were 0.225±0.022, 0.214±0.059, 0.219±0.061 and 0.220±0.103 h-1, there was no significant difference; the Ka of different gender(male and female) were 0.237±0.168 and 0.223±0.172 h-1, and there was no significent difference.When GFI was incubated in the environment of 37℃, the concentration of different p H( 3.5, 5.0, 5.8, 7.0, 7.8 and 9.0) was degraded to 98.6, 96.7, 95.8, 81.2, 41.7 and35.8%of the original concentration.Conclusion:GFI has a wide window absorb throughout the intestines, and the mechanism of the absorbtion was passive transport. The perfusion rate and p H had a significant influence in the Ka, and GFI was more stable in the environment of acidic than in base.