| Objective: To estabilish an accurate and sensitive HPLC method for the determination of dipyridamole and acetylsalicylic acid in human serum;To investigate the phannacokinetics and bioequiavailability of sustained-release compound tablets of aspirin-dipyridamole in China healthy volunteers, sustained-release compound tablets(ST) of aspirin-dipyridamole and regular tablets(RT) of aspirin and dipyridamole after single and multiple dose were orally administrated to healthy volunteers in randomized crossover and two cycle design;To compare speed and degree of absorption and Css of sustained-release compound tablets and regular tablets of aspirin after single and multiple dose and to inspect the characteristic of sustained-release compound tablets of aspirin-dipyridamole and to provide evidence for clinical practics.. Methods: 1.20 healthy volunteers were enrolled in the study of single oral administration of ST and RT. All subjects were randomly divided into two groups, balanced by body weight. Clinical symptoms, vital signs, electrocardiogram, routine blood test, routine urine test, prothrombin time and blood biochemical test of all volunteers were recorded and evaluated before and after single oral administration of ST and RT. 2. The two groups healthy volunteers were enrolled in the study of multiple oral administration of ST and RT. The clinical-symptoms, vital signs, electrocardiogram, routine blood test, routine urine test, prothrombin time and blood biochemical test of all volunteers before and after multiple oral administration of sustained-release compound tablets of aspirin-dipyridamole (aspirin50mg,dipyridamole400mg, qd, for 7 days) and regular aspirin (50mg, qd, for 7 days) and dipyridamole (400mg, qd, for 7 days) were recorded and evaluated. 3. Pharmacokinetics study. A sensitive and rapide HPLC method was developed to determine the serum samples concentration and the pharmacokinetic parameters of acetylsalicylic acid and dipyridamole were calculated by DAS software, and the adverse reaction, ifany, was recorded at same time.Results: 1. The detection limit of dipydamole in serum was 0.5 w gjnl"1, with a good linearilty in the range of 0.05~8ng.ml'1(r=O.9998). The raletive recovery was above 80%~105%. The detection limit of acetylsalicylic acid in serum was 0.2 u g.ml'!, with a good linearilty in the range of 0.1~8ng mr'(r=0.9999). The relative recovery was above 80%~100%. 2. The main pharmacokinetic parameters of dipyridamole of ST and RT after single dose were as follows: t\a 14.660±1.40h and 13.627±1.70h, Cmax 4.045±l.27fig ml'and 5.201±0.99ng ml"1, Tmax 2.93±0.34h and 2.10± 0.26h, AUQm 53.950±6.70ng.h.ml"1 and 52.712±7.09 155.525±6.97ng.h.mr' and 57.118±7.28ng.h.ml1. The relative bioavailability of dipyribamole of ST was found to be 102.756±7.18%. 3.The main pharmacokinetic parameters of acetylsalicylic acid of ST and RT after sigal dose were as follows:ti/2 2.599±0.325h and 2.662±0.288h, Cmax 4.412iO.831ug.ini"1 and 4.033i0.679ug.ml~1, Tmax 1.500±0.281h and 2.447±0.229h, AUC |
PDF Full Text Request