Comparison of Different Quantitative Methods in Bioavailability Studies of Theophylline Anhydrous Retard Tablets

• Main Authors: Shu-Ming Chang, 張書銘
• Other Authors: Cheng-Hsiung Liu
• Format: Others
• Language: zh-TW
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/10391145017723382949

碩士 === 中國醫藥學院 === 藥物化學研究所 === 89 === Abstract The theophylline is a drug for controlling asthma in clinical therapy. Since the therapeutic range is relatively narrow and the process in body is influenced by individual and environmental factors very much. Therefore development of sustained release formulation can provide more stable theophylline concentration and long action of the drug. In this study, it was mainly estimating relative bioavailability in Taiwanian and the analysis results of two quantitative methods (HPLC and FPIA) of the sustained release formulations of test preparation (Theolin SR®) and reference preparation (Euphyllin retard®). Twelve healthy subjects received both products by randomized two-way crossover design. Within six days, each subject was administrated 250mg doses every 12 hour. The plasma samples were collected all day only on the first and sixth day. The concentrations of theophylline in plasma samples were analyzed by high performance liquid chromatography (HPLC) system. The conditions of the system were RP-18e column, acetonitril: water with phosphoric acid (pH 3.88) = 6:94 (v/v) and monitored at UV 272 nm. The same samples were also analyzed by fluorescence polarization immunoassay (FPIA) method. These methods showed good linearity, the intra- and inter-day validation and limit of quantification were reasonably with C.V. values less than 10%. The relative recovery was above 95%. The results showed Taiwanian reaching peak concentration (4.1 μg/ml) at about 9.8 hours after first oral administration of theophylline sustained release tablet. The mean half-life was about 8.2 hr. Estimation of steady-state pharmacokinetics parameters of two products were included area under the curve of dose interval (AUCssτ), time of peak concentration (Tssmax), peak concentration (Cssmax), trough concentration (Cssmin), average concentration (Cssavg), fluctuation (PTF%) and so on. After analyzed by two-way ANOVA statistics, there was no obviously statistic difference in relative parameters. Both of products were well bioequivalence by biological. With regard to comparison of two quantitative methods, the correlation of plasma samples concentration was up to 0.99. The results parameters were analyzed by paired t-test, the same drug product was analyzed by two quantitative methods still have obviously statistic different in AUCssτ, Cssmax, Cssmin, Clss/F relative pharmacokinetics parameters.