Compound Irbesartan Dispersible Tablets Bioequivalence And Protein Binding Studies

1. Determination of irbesartan and hydrochlorothiazide in human plasma and bioequivalence assessment of the compound tablets and dispersible tabletA new method for determination of irbesartan and hydrochlorothiazide in human plasma and to conduct bioequivalenee study of compound irbesartan and hydrochlorothiazide tablets in human plasma has been established.A single oral dose of compound irbesartan and hydrochlorothiazide tablets and dispersible tablet was given according to a randomized crossover design. The plasma concentation of irbesartan and hydmehlomthiazide were determinde by a performance liquid chromatography and high performance liquid chromatography-mass spectrometry method .The main pharmacokinetic parameters of the test and the reference tablets were as follows: Irbesartan: t_maxwere (1.8±0.7) and (1.7±0.6) h, C_max were (1204.6±340.5) and (1252±295.3) ng·mL^-1, t_1/2 were (5.8±4.6) and (6.6±7.3) h, AUC_0-t were (9053±4132) and (9852±4337 ) ng·h·mL^-1, AUC_0-∞,were (10524±5263) and (11607±5842) ng·h·mL^-1, The relative bioavailabiliry of the test formulation was (94.2±21.3)%.Hydrochlorothiazide: C_max were (72.6±33.8) and (74.7±31.9)) ng·mL^-1, _tmax were ( 2.0±0.5) and (1.8±0.4) h, t_1/2 were (2.9±1.2) and (2.5±1.0) h, AUC_0-48were (372.3±168.7) and (377.5±210.4) ng·h·mL^-1, AUC_0-∞were (398.3±191.2) and (396.5±223.5) ng·h·mL^-1, respectively. The relative bioavailabiliry of the test formulation was (106.7±26.1) %. The test compound tablets were of bioequivalenee .There were no significant difference between preparations and periods of C_max and AUC by ANOVEA, two one-side t-test and (1-2α) confidential interval test, and t_maxby Wilcoxon's non-parameter rank-sum test. This showed that the two preparations were bioequivalence.2. Study of the effect of hydrochlorothiazide on protein-binding rate of irbesartanThe effect of hydrochlorothiazide on protein-binding rate of Irbesartan was detemined , equilibrium dialysis and HPLC were emploryed to measure the concentration of free drug . it has been carried out on a DiamonsilC₁₈ (200 mm×4.6 mm, 5μm) column with UV detection at 225 nm. mobile phase was acetonitrile-monobasic potassium phosphate solution (45:55, v/v ) . flow rate was set at 1.0 mL·min^-1and the column temperature was 35℃. Protein binding rate of irbesartan was 93.8% and 92.5% respectively when incubated without and with hydrochlorothiazide.