| Objectives:1. To establish an high-performance liquid chromatography method for the determination of aminophylline in human blood.2. To study the pharmacokinetics and relative bioavailability of aminophylline sustained-release tablets in healthy volunteers and to evaluate the absorption, distribution, elimination characteristics.3. To investigate the possible factors affecting the absorption, distribution and elimination of aminophylline based on the drug concentration in blood and therapeutic effects in patients treated with aminophylline. which will provide an experimental basis for its reasonable clinical applications.Methods:1. The aminophylline in blood was determined by high performance liquid chromatography,with AGT Venusil XBP-C18 (3.9×150 mm)column and mobile phase of water-methanol (80:20, V/V);at flow rate of 1.0 ml/min.The injection volume was 20μl, column temperature was 28℃,and the detection wavelength was 270nm.2. Test design strategy:A two-cycle cross-over test was designed.20 healthy male volunteers were randomly divided into two groups as aminophylline sustained-release tablets test or reference.A liqut of biood was collected before and 1,2,3,4,4.5,5,5.5, 6,7,8,12,24,36h after, orally taken test or reference and immediately moved into tubes with heparin. The biood was centrifuged at 5000rpm for 5min and plasma were taken out and stored at-20℃for analysis.The aminophylline level in plasma was determinated by established HPLC. The aminophylline concentrations-time was processed by "DAS 2.0", and pharmacokinetic parameters for both test and reference preparations were calculated. The bioequivalence between test and reference preparations were evaluated through analysis of variance, two-sided t-test and (1-2α) confidence interval analysis.3. The plasma concentrations of aminophylline of 10 aminophylline heated patients were collected and analysed. and the possible factors affecting aminophylline absorption, distribution and elimination were evaluated.Results:The major pharmacokinetic parameters for test and reference formulations of aminophylline sustained-release were as follows 9.131±1.944h and 9.851±1.787 h, respectively; Tmax were 3.950±0.560h and 4.100±0.528h; Cmax were 3.660±0.697μg/ml and 2.686±0.374μg/ml; AUC0-36 were 41.014±7.329μg/ml/h and 39.355±6.235μg/ml/h; AUC0～∞were 44.293±8.595μg/ml/h and 43.323±7.362μg/ml/h, respectively. The relative bioavailability (F) for test preparations of aminophylline slow-release tablets was 105.0%±16.7%.Conclusions:1. A rapid, sensitive and accurate HPLC method was established, and applied for the determination of aminophylline level in human blood.2. The relative bioavailability (F) in volunteers for test preparations of aminophylline sustained-release tablets was 105.0%±16.7%.3. Multi-factor analysis of variance showed that there was no significant difference both between preparations and periods for the major pharmacokinetic parameters.The double-sided t-test and confidence interval analysis (1-2α) for individuals, periods or preparations were consistent with the assumption,and the aminophylline sustained-release tablets of test and commercially available reference are bioequivalent preparations.4. From the serum concentration and the clinical efficacy of the 10 cases of patients treated with aminophylline,it could be concluded that the sampling method and aminophylline concention in this study may trueiy reflect,and it's unrational use were exist in some way,and it's individualized administration is needed.
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