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The Effect of Marine Sulfated Polysaccharide 916 on CYP450 Subtype Enzymes and Their Sexual Differences

Author: YuZuoJie
Tutor: LvZhiHua
School: Ocean University of China
Course: Medicinal Chemistry
Keywords: 916 CYP450 Subtypes Affect Gender differences
CLC: R96
Type: Master's thesis
Year: 2009
Downloads: 151
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Abstract

Marine sulfated polysaccharide 916 marine chitin-based raw materials, multi-step molecular modification from a poly anionic sulfate glycosaminoglycans. System pharmacodynamic studies have shown that 916 has good anti-atherosclerotic activity. Liver drug metabolizing enzymes including phase I enzymes (cytochrome P450) and phase II enzymes. The functional status of the liver phase I enzymes have a significant impact on drug efficacy and toxicity. Closely associated with drug metabolism in human liver cytochrome P450 (CYP450) Isoform there is CYP1A2, CYP3A and CYP2E1. Clarify the drug induction or inhibition of CYP450 and this effect whether there are gender differences in the pharmacokinetics of the drug research, drug safety evaluation, the interaction between the drugs in the prevention of clinical medicine and clinical dosing regimen design has a very important significance. Europe and the United States have been CYP450s and its isoenzyme determination for the screening of new drugs and metabolic studies, and put it as a new drug application must be carried out a pilot. This research uses the probe drugs caffeine, dapsone, Chlorzoxazone, the overall test of the sub-rat, rats vitro in two ways, through drug metabolism pharmacokinetic parameters evaluated 916 pairs CYP450 isoforms CYP1A2 CYP3A, CYP2E1 induction or inhibition, and this effect is the existence of gender differences, so that the full range of this new drug safety evaluation and provide a reference for its clinical use of drugs. Caffeine, dapsone and chlorzoxazone three probe school visits, drug recovery, precision, sensitivity HPLC method that can be used as \Overall test part through the blank control group and 916 induced group of three probe drugs caffeine, dapsone, Chlorzoxazone of drug curves and drug pharmacokinetic parameters investigated marine sulfated polysaccharide 916 male and female rats CYP450 The subtype CYP1A2, CYP2E1, CYP3A metabolic enzymes. Part vitro using liver microsomes were incubated in vitro method, obtained by in vitro incubation of rat liver microsomes control group and 916 treated group, respectively, the three probe drugs liver microsome concentration - time curve calculated in vitro to eliminate rate, compared to study marine sulfated polysaccharide 916 in male and female rats in vitro CYP450 isoforms CYP1A2, CYP2E1, CYP3A metabolic enzymes. In vitro and in vivo test results have proved that marine sulfated polysaccharide 916 pairs of the same sex rat liver microsomes CYP450 isoforms 1A2, 2E1, 3A no significant induction or inhibition. 916 metabolism and toxicity evaluation, safety evaluation provide important clues to provide a theoretical basis for its clinical trials and applications.

The Effect of Marine Sulfated Polysaccharide 916 on CYP450 Subtype Enzymes and Their Sexual Differences

Abstract

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