Study on the pharmacokinetics and bioequivalence of isosorbide 5-mononitrate and aspirin from compound isosorbide mononitrate sustained release tablets in healthy volunteers

OBJECTIVE To study the pharmacokinetics and bioequivalence of isosorbide 5-mononitrate and aspirin from compound isosorbide mononitrate sustained released tablets in healthy volunteers.METHODS Isosorbide mononitrate sustained release tablets and aspirin enteric-coated tablets were used as the reference preparations.In a randomized crossover design,single and multiple doses of test and reference preparations were given to 20 and 18 healthy male volunteers respectively. Isosorbide-5-mononitrate and salicylic acid concentrations were measured by ESI-MSD and DAD respectively. RESULTS After a single oral administration,the pharmacokinetic parameters of isosorbide 5-mononitrate test and control preparations were as following:AUC_~0→36 h (10 025.1±1 336.9) and (9 472.0±1 139.3)μg·h·L~-1 ;t_~max (4.7±1.0) and (4.5±0.8) h;c_~max (661.9±76.5) and (658.0±83.2) μg·L~-1 , respectively. For salicylic acid, the pharmacokinetic parameters were as AUC_~0→∞ (21 864±6 239) and (18 872±5 379) μg·h·L~-1 ;t_~max (0.8±0.4) and (4.7±1.0) h;c_~max (6 050±1 133) and (3 797±872)μg·L~-1 ,respectively. The relative bioavailability of isosorbide 5-mononitratte and salicylic acid were (105.9±6.4)% and (117.5±19.3)%,respectively. After multiple oral administration of test and reference preparations,the pharmacokinetic parameters were as following:AUC_~ss (10 333.5±1 519.2) and (10 410.5±1 767.5) μg·h·L~-1 ;t_~max (4.3±1.1) and (4.3±0.8) h;c_~max (724.8±95.5) and (786.7±110.0) μg·L~-1 ;c_~min (129.4±40.0) and (121.9±36.0) μg·L~-1 ;c_~av (430.6±63.3) and (433.8±73.6) μg·L~-1 ; DF (140.1±15.9)% and (155.2±20.7)%,respectively. The relative bioavailability of isosorbide 5-mononitrate was (100.5±13.0)%. CONCLUSION Compoud isosorbide mononitrate sustained release tablets showed bioequivalence for the isosorbide 5-mononitrate component with the reference preparation, and the AUC for the aspirin component was bioequivalent with that of the reference drug,but the test drug was more rapidly absorbed.