| Marine Sulfated Polysaccharide 916 was authorized to go into clinical study further by National Drug and Foods Administration at the name of I level new drug with activity of anti-atherosclerosis . Drug combination is usually used for cardiovascular disorder clinically, to combine with other drug, drug interaction must be considered in development of new drugs. Lovastatin (LV) is the inhibitor of HMC-CoA and can inhibit synthesis of endogenous cholesterol and can heal atherosclerosis like 916. There are few domestic reports about pharmacokinetic interaction. This paper chose LV as model drug and 916 as combined drug to study the diversity of pharmacokinetics parameter of LV in rats after a single oral does of LV alone and with 916 together. This paper also investigated the influence of metabolism of LV in liver- microsome caused by 916.1.In this paper,an analytical method in biological sample was developed by HPLC: chromatography was carried out using a XTerra? MS C18 column (150×2.1mm, 5μm) with a mobile phase consisting of acetonitrile-water(63:37, v/v) at a flow rate of 0.2 ml/min and 35℃as temperature of column. The calibration plots of LV in biological sample were linear over a range from 0.01 to50 mgL-1, R2 were all exceed 0.99; LOQ of LV in plasma and urine were about 0.01 mgL-1; extract recovery of LV in plasma was more than 80%; the analytical precision of intra-day and inter-day were less than 15%. This analytical method is simple, high sensitive and high reduplicative enough to be used in this pharmacokinetic study.2. To investigate the pharmacokinetics of LV in rats, LV was administered alone or in combination with 916. When in combination with 916, the plasma concentration of LV in male rats, t1/2 was changed from 4.2±0.8h to 2.5±0.5h, AUC0→∞was changed from 763.0±58.0h·μg·L-1 to 3678.7±1445.4h·μg·L-1,Cmax was changed from 173.2±32.4μg·L-1 to 1333.1±211.4μg·L-1, the changes were all conspicuous (P<0.05); in female rats, t1/2 was changed from 5.9±2.1h to 3.6±0.5h, AUC0→10 was changed from 397.0±95.5h·μg·L-1 to 561.56±167.37h·μg·L-1(P<0.05).3. To investigate the elimination of LV from male rats urine and fecal by after a single dose of LV, metabolism cages method was used. The results showed that the accumulated excretive ratio of unchanged LV was 5.95% from urine,46.26% from fecal for 74h after dosing,and LV almost was indiscoverable in urine after 74h after dosing .When co-administered with 916,the elimination of LV from urine during 0~10h and 0~24h decreased significantly (P<0.05), but there were no significant changes by fecal(P>0.05).4. To investigate the metabolism of LV from male rat liver-microsome after a single dose of LV, metabolism of liver-microsome in vitro method was used. The result showed the metabolism velocity of LV was linear over a range from 0 to 60 min, the metabolic velocity of LV decreased over 60-90min. There were no significant changes when 916 was co-incubated.5. To investigate the influence of metabolism of caffeine, dapsone and chlorzoxazone in liver-microsome of rats caused by 916, P450 probe assays was used. The results show 916 have neither notable induced nor inhibitive effect on CYP1A2, CYP2E1, CYP3A enzymes.
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