|
Spironolactone (spironolactone) chemical structure similar to aldosterone, the earliest use of aldosterone receptor antagonist commonly used in clinical accompanied aldosterone elevated intractable edema, congestive heart failure, high blood pressure, and so on. For a further understanding of the physiology and pathology of aldosterone, thus the study of the pharmacological effects of spironolactone further deepen its broader prospects for clinical application. Spironolactone lower the blood concentration in the human body, faster metabolism, its metabolites Canrenone (canrenone) Canrenone pharmacokinetic study no report. Spironolactone tablets spironolactone tablets in order to the Jiangsu Yixing advance pharmaceutical factory production standard reference formulation, Jiangsu Yangtze River Pharmaceutical Co., Ltd. developed for test preparation, by measuring the concentration of metabolites of spironolactone Canrenone two reagents relative biological bioavailability and bioequivalence studies, to provide a reference for the clinical use of spironolactone. Objective To study Canrenone pharmacokinetics in healthy volunteers and relative bioavailability degrees. Method using two-period crossover trial design, 18 subjects were randomly divided into 2 groups, respectively, oral spironolactone standard reference preparations and preparations doses are 200mg two test intervals of two weeks. Subjects before the test examination of liver, renal and cardiac function were normal. Volunteers, and family history of investigation, I and family without allergies, the unused test before two weeks and test any other drugs and ban alcohol and tobacco. The subjects test Qianri Wan 8:00 fasting 200mL warm water next morning delivery service tested drugs. Medication 4h into the same low-fat, low-protein standard meal. Administration 0.5,1,1.5,2,2.5,3,4,6,8,12,24,48,72 h after administration of venous blood 4mL, heparin, centrifuged 10min (3000r/min) , take the plasma to be tested at -20 ℃. Using high-performance liquid chromatograph analysis of drug concentrations: Precision to draw plasma 1.0mL ethyl acetate was added 4mL vortex mixed-5min, the Centrifugal 10min (3500r · min -1 ), draw the upper organic phase 3mL ; drying at 40 ° C water bath and nitrogen, with 100μL of methanol: water = 8:2 was dissolved, 40μL injections. The color \u0026 Poor conditions of the the chromatograph column: Column: AligentC 18 column (5μm, 4.6mm × 200mm), mobile phase: acetonitrile: 0.02M diammonium phosphate solution = 45:55 (v / v ); flow rate: 1.0mL/min diode array detector, wavelength: 280nm Injection amount: 40μL. Concentration-time data using 3P97 software, computer processing, according to the F-test and AIC value selection atrioventricular number value for goodness of fit (goodness of fit) choice of weights. Plasma peak concentration (C max ), take the time to peak (T max ) Found. Results of this study examine the Franco-Prussian High performance liquid chromatography (HPLC) Canrenone Canrenone pharmacokinetics in the human body, the the methodological study results show that the method is specific impurities in the plasma does not interfere with the sample measurement; The standard curve regression equation: C = 0.7671A 3.3992 (r = 0.9999), the linear range 9.375 ~~ 300μg · L -1 . Both recoveries, poor days, the day difference are in line with the analysis of biological samples. The study shows that the one-compartment open model Canrenone process in line with the body in healthy subjects. The two formulations main pharmacokinetic parameters were as follows: T max (4.2 ± 1.2) h and (4.7 ± 1.6) h, C max , respectively (159.8 ± 46.6 ) μg · L -1 and (149.7 ± 43.4) μg · L -1 T 1/2ke were (18.18 ± 4.88) h and (19.07 ± 3.88) h, the the AUC 0 t , respectively (3168.5 ± 688.4) μg · h · L -1 and (3266.7 ± 626.9) μg · h · L -1 , AUC 0 ∞ , respectively (3610.7 ± 768.4) μg · h · L -1 and (3758.9 ± 641.9) μg · h · L -1 . Compared with the standard reference preparation, test preparation relative bioavailability F 0 t (106.3 ± 26.0)% F 0 ∞ (107.6 ± 25.9)%. The on the the AUC between the two formulations 0 t , AUC 0 ∞ The C max analysis of variance and two one-sided t-test, etc., T max using non-parametric method tests show that the two formulations are bioequivalent. Conclusion 1. Reveals the the healthy volunteers Canrenone pharmacokinetic characteristics. 2. Jiangsu Yangtze River Pharmaceutical Co., Ltd. developed spironolactone tablets with standard reference formulations are bioequivalent.
|