Pharmacokinetics of fluvastatin sodium sustained-release tablets

Absorbing healthy volunteers took fluvastatin solution on an empty stomach, and it absorbed quickly (98%). After oral administration of fluvastatin sodium sustained-release tablets, compared with capsules, the absorption rate of fluvastatin was delayed by 60%, and the average retention time in vivo was prolonged by nearly 4 hours. If you eat, the absorption rate of the drug decreases. The distribution of fluvastatin mainly acts on the liver, which is also the main organ of its metabolism. Calculated from the whole body blood concentration, the absolute bioavailability is 24%. The apparent distribution volume (Vz/f) of fluvastatin is 330 liters. More than 98% of circulating drugs are bound to plasma protein, which has nothing to do with the plasma concentrations of fluvastatin, warfarin, salicylic acid and glibenclamide. Metabolism Fluvastatin is mainly metabolized in the liver. The circulating drugs are mainly fluvastatin prototype and N- diisopropylpropionic acid, a metabolite with no pharmacological activity. Hydroxylated metabolites have pharmacological activities, but they do not enter the systemic blood circulation. The metabolic pathway of fluvastatin in human liver has been clarified, and the biotransformation of fluvastatin is completed through a variety of cytochrome P450(CYP450) pathways. Inhibition of cytochrome P450 has little effect on fluvastatin metabolism, and inhibition of cytochrome P450 is the main reason for drug interaction. Some in vitro experiments have studied the inhibitory effect of fluvastatin on cytochrome P450 isoenzymes. Fluvastatin can only inhibit the metabolism of compounds metabolized by CYP2C9. This suggests that there may be competitive interactions between fluvastatin and compounds based on CYP2C9, including diclofenac, phenytoin, tolbutamide and warfarin, but there is no clinical data to confirm it. After healthy volunteers took 3H labeled fluvastatin, about 6% of the radioactivity in urine and 93% in feces were eliminated, and the discharged fluvastatin only accounted for less than 2% of the total labeled amount. The plasma clearance rate (CL/f) of fluvastatin was 65438±0.8±0.8l/min/min min. The steady-state plasma concentration of fluvastatin 80mg/ day has no accumulation effect. There is no significant difference in AUC between fluvastatin taken at the same time with dinner and fluvastatin taken 4 hours after dinner. Pharmacokinetics Under the special circumstances of the general population, the plasma concentration of fluvastatin does not change with age and sex. However, it was found that the response to its treatment was enhanced among women and the elderly. Because fluvastatin is mainly excreted through bile, it has obvious biotransformation before entering the systemic circulation, so the possibility of drug accumulation cannot be ruled out in patients with liver dysfunction. (See Drug Interaction and Precautions)