Compound irbesartan dispersible tablets bioequivalence protein binding
|School||Shenyang Pharmaceutical University|
|Keywords||Compound irbesartan dispersible tablets Irbesartan Hydrochlorothiazide Bioavailability Equilibrium dialysis|
1. Compound irbesartan dispersible tablets bioequivalence create a more agile and efficient HPLC and LC-MS analysis in human plasma irbesartan and hydrochlorothiazide thiazide drug concentration. And by measuring the concentration of the drug at different times in human plasma, study test formulation compound irbesartan dispersible tablets and reference preparation of compound irbesartan tablets drug kinetic parameters and biological utilization, evaluation of different manufacturers produced whether the two drugs are bioequivalent to provide a basis for the clinically safe and effective medication. Test uses the design of the crossover single oral dose administration, data processing by DAS 2.0 software, test formulation of compound irbesartan dispersible tablets and reference preparations irbesartan hydrochlorothiazide tablets irbesartan pharmacokinetics pharmacokinetic parameters were: t max were 1.8 ± 0.7 (mean ± standard deviation, the same below), and 1.7 ± 0.6 h, C max sub > were 1205 ± 340.5 and 1252 ± 295.3 ng · ml -1 sup> t 1/2 5.8 ± 4.6 and 6, respectively. 6 ± 7.3 h, calculated using the trapezoidal rule, AUC 0-t were 9053 ± 4132 and 9852 ± 4337 ng · h · ml -1 sup>, AUC 0 - ∞ were 10524 ± 5263 and 11607 ± 5842 ng · h · ml -1 sup>, AUC 0-t , with reference preparation compared the relative bioavailability of the test formulation irbesartan (94.2 ± 21.3)%, variance analysis showed that the test formulation and compared to the reference formulation, bioavailability was no significant difference (P lt; 0.05). Test formulation of compound irbesartan dispersible tablets and reference preparations irbesartan hydrochlorothiazide tablets hydrochlorothiazide thiazide the main pharmacokinetic parameters were 2.0 ± 0.5: t max and 1.8 ± 0.4 h, C max were 73.6 ± 33.8 and 74.7 ± 31.9 ng · ml . -1 sup>, t 1/2 , respectively, 2.9 ± 1.2 and 2.5 ± 1.0 h, AUC 0-t were calculated using the trapezoidal method 372.3 ± 168.7 and 377.5 ± 210.4 ng · h · ml -1 sup>, AUC -- ∞ were 398.3 ± 191.2 and 396. 5 ± 223.5 ng · h · ml -1 sup>, AUC 0-t , with the reference formulation compared to the relative bioavailability of the test preparation hydrochlorothiazide average (106.7 ± 26.1)%, variance analysis showed that the test formulation and reference formulation compared to the bioavailability was no significant difference (P lt; 0.05). Two formulations of irbesartan and hydrochlorothiazide AUC and C max values ??by logarithmic transformation, analysis of variance, analysis of two one-sided t-test and 90% confidence interval, t max by non-parametric Wilcoxon's rank sum test, the results show that there was no significant difference in the preparations and during the week, so the two formulations are bioequivalent. 2. Hydrochlorothiazide irbesartan protein binding affect the determination of hydrochlorothiazide irbesartan protein binding. Equilibrium dialysis method combined with high performance liquid chromatography to measure the concentration of free drug, by using Diamonsil C 18 (200 mm × 4.6 mm, 5μm) column, acetonitrile - potassium dihydrogen phosphate 10 mmol · L -1 sup> (pH 3.5) with phosphoric acid (45:55, v / v) as the mobile phase, detection wavelength: 225 nm, flow rate: 1.0 mL · min - 1 sup>, column temperature: 35 ° C. Comparison not containing added protein binding of irbesartan and hydrochlorothiazide. Not containing added protein binding of irbesartan and hydrochlorothiazide, respectively, 93.8% and 92.5%. Hydrochlorothiazide irbesartan protein binding.