| Pravastatin (PV) is a cholesterol-lowering inhibitor of hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis, has been indicated for the treatment of hypercholesterolemia and the prevention of cardiovascular disease, diabetes mellitus, and renal disease. Marine Sulfated Polysaccharide 916 has been reported with good anti-atherosclerosis activity and authorized to go into clinical study as I level new drug by National Drug and Foods Administration. In order to treat combined hyperlipidemia, statins species and other cholesterol-lowering drugs are usually used together for treating patients. In order to provide reference about safety medication in clinic, the influences of 916 on the pharmacokinetics of PV in rats were studied.1. To detect PV in biological samples, high performance liquid chromatography analysis method was established. In this paper, protein precipitation by acetonitrile combined with SPE method is selected for the pretreatment of biological samples. The analysis was performed using a C-18 reverse-phase column with mobile phase of Na2HPO4 buffer solution (pH=3.0) and acetonitrile. The precision, reproducibility and recovery of PV in biological samples were tested. This method was proved to have high sensitivity, the precision and reproducibility was better. This method can be used to detect the concentration of PV in plasma, liver and muscle.2. The influence of 916 on the pharmacokinetics of PV in male and female rats was investigated. When in combination with 916 , the highest plasma concentration(CMax) of PV were decreased than those when PV was administered alone(P<0.05), but AUC0→∞was not significantly effected (P>0.05). Meanwhile in male rats, t1/2 was increased, ke was decreased (P<0.05), but in female rats, t1/2 and ke weren't changed significantly (P>0.05).3. To explore the influence of 916 on the intestinal absorption of PV, the rat intestinal recirculating method in situ was utilized. When in combination with 916, the absorption Constants (Ka) was lower than those when PV was administered alone (P<0.05), but the percent absorption was not significant effected (P>0.05).The results suggested that 916 had effects on the rate of absorption of PV from the intestine, delayed the absorption of PV, but the total percent absorption wasn't significant effected.4. The influence of 916 on the distribution of PV in liver and muscle was investigated. When in combination with 916,the concentration of PV in liver at 0.4h was significant decreased(P<0.05), the concentration of PV in liver at 1.5h was not significantly effected (P>0.05) , but the concentration of PV in liver at 4h was significantly increased. The concentration of PV in muscle was not significantly effected (P>0.05).
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