The Effect Of Marine Sulfated Polysaccharide 916 On CYP450 Subtype Enzymes And Their Sexual Differences

Marine sulfated polysaccharide 916 is a new form of sulfated amino polysaccharide that is derived from marine chitin and by ways of molecular modifications. 916 shows good antiatherosclerotic activity.Hepatic drug metabolizing enzyme include Phaseâ… enzyme (Cytochrome P-450) and Phaseâ…¡enzyme. The functional state of drug metabolizing enzymes is an important determinant for drug activity as well as toxicity. In human liver, CYP1A2, CYP3A and CYP2E1 are the most important enzymes subtypes of CYP450, which play a critical role in drug metabolism.It is very useful for its pharmacokinetics study, its safety assessment and the prediction of the inter-drug interaction associated with them to investigating its influences (induction or inhibition) on CYP450 enzymes, especially its sex-based differences. By far, the assay of CYP450 and its isoenzymes was used in the selection of novel drugs and metabolic study in Europe and American, it is also the compulsory test in the novel drug application.This study investigated 916's influence on CYP1A2, CYP2E1 and CYP3A enzymes, especially their sex-based differences, through comparision of pharmacokinetics data of Caffeine, Chlorzoxazone and Aminophenylsulfone, which are the special probe drugs for CYP1A2, CYP2E1 and CYP3A. This study was carried out by two aspects: in vivo and in vitro in rats. Then the assessment to the drug's safty and the design of drug administration would be more roundly.Caffeine, Chlorzoxazone and Aminophenylsulfone were demonstrated as the probe drugs of the"Cocktail"approach in the study of effect of 916 on CYP450 subtype enzymes through the assessment of the HPLC experimental method, which includes the selectivity, intraday and inter-day reproducibility, and the detection limits.In vivo the effect was studied through concentration-time curve and pharmacokinetic parameters of the three probe drugs. In vitro study, liver microsome incubation was adopted. The results in vivo and in vitro showed that 916 had no effect on the activity of CYP1A2, CYP2E1 and CYP3A enzymes. The study provides an important clue for the metabolism research, toxicity assessment and safety assessment of 916.