Study On Bio-Activity And Metabolism Of Polysaccharide Sulfates-Containing AZT In Animal Body

In this article, at first we have mainly succeeded to synthesize polysaccharide sulfates containing AZT from water-soluble starch. 3'-azido-3'-deoxy-5'-O-succinyl-thymidine(5'-Suc-AZT) was obtained by reaction of 3'-azido-2'3'-dideoxythymidine(AZT) and Succinic anhydride in Pyridine, catalyzed by 4-Dimethylaminopyridine(DMAP). Starch containing AZT was obtained by reaction of 5--Sue-AZT and water-soluble starch in DMSO, catalyzed by DMAP and N,N -dicyclohexylcarbodiimide (DCC). Aftersulfated by SO3 ?Py, we obtained polysaccharide sulfates containing AZT withDSAZTT=0.1-0.22, DSsu1=1.0~1.85 and Mn=1.13~1.47 ?104. Structuredetermination of every step reaction were discussed in the article.In order to clarify the pharmacokinetic characteristic of AZT-SSP and to guide the use of clinical drug aright,we studied the pharmacokineticparameters of AZT-SSP using Ultraviolet (UV) in rats and mice given drugintravenously and orally administration. At the same time, SSP given intravenously to mice, conduct acute toxicity experiment to get security dose and the concentration of blood drug was fell off and distrabuted rapidly.The measurement of AZT-SSP in animal serum samples was achieved by Ultraviolet method.The method was sensitive ,specific and simple enough todetermine the cocentration of AZT-SSP metabolite and to obtain pharmacokinetic parameters.AZT-SSP was metabolized very fast in animals,and its elimination half-life in body was very short. The distribution in liver, lung and spleen was more, muscle was less and the other tissues was between the former and the latter. Given AZT-SSP to rats by orally administration , then have measured the contentes of CHO,TG,GLU with Auto-Biochemistry Analysis.As a result,SSP appreciably increase TG's content in rats' serum.AZT-SSP was metabolized very fast.After intravaenous administration of AZT-SSP into mice,the metabolite appeared immediately and its peak time was 15min approximately,then it was eliminated slowly.After oral administration of AZT-SSP to rats, the concentration of the metabolite in serum was still very high and its peak time was at 30min,then it was eliminated slowly.We foud out that the ultraviolet absorption spectrophotometry of the metabolite was similar to that of AZT-SSP.The maximal absorption wavelength of the metabolite was at 267nm. AZT-SSP may be decompound very fast in bodies of animals,and the metabolise was eliminated slowly.