Pharmacokinetics and relative bioequivalence of compound paracetamol, aspirin and caffeine tablets in healthy volunteers

Objective: To develop an HPLC method for simultaneous determination of paracetamol, salicylic acid and caffeine in human plasma and to investigate the pharmacokinetics and bioequivalence of test and reference paracetamol, aspirin and caffeine tablets in human. Method:A randomized crossover design was performed in 20 healthy volunteers. Plasma samples treated with ethyl acetate extraction were separated on a phenyl column with a mobile phase of methanol - ammonium acetate buffer (25: 75 ) and detected at 237 nm. Results: The main pharma- cokinetic parameters of C_(max), T_(max), t_(1/2) (λ_Z), MRT and AUC_(0-24) after po two test or reference paracetamol, aspirin and caffeine tablets for paracetamol were (9.02±1.55) and (8.25±2.33) μg·mL~(-1), (0.70±0.20) and (0.70±0.20)h, (4.01±0.49) and (3.81±0.76)h, (4.81±0.52) and (4.86±0.86)h,(31.54±4.79) and (30.39±5.88)h·μg·mL~(-1), respectively; for salicylic acid (active metabolite of aspirin) were (42.60±9.20) and (32.74±7.83)μg·mL~(-1), (1.20±0.50) and (3.0±1.4) h,(2.95±0.73) and (2.87±0.55) h, (5.52±0.91) and (6.17±1.00)h, (254.82±58.90) and (244.93±56.80)h·μg·mL~(-1), respectively;for caffeine were (3.80±0.60) and (3.93±1.09)μg·mL~(-1), (0.90±0.30) and (0.90±0.60)h, (7.23±3.41) and (6.16±3.07)h, (9.49±3.60) and (8.76±3.77)h, (23.43±5.65) and (25.24±7.51)h·μg· mL~(-1), respectively. The relative bioavailability of the test tablets were (107.5±28.0)%, (109.2±39.4)%,(99.2±40.0)% for paracetamol, salicylic acid and caffeine, respectively. The results of ANOVA and two one-sided t-test showed that there was no significant difference between the two formulations in the AUC_(0-24) and C_(max)·Conclusion: The HPLC method is proved to be selective and sensitive. The two formulations are bioequivalent.