| 摘要: | 中 文 摘 要 Amikacin是供注射用之半合成胺基糖甘類抗生素，臨床用於治療尿路感染、敗血症、皮膚軟組織感染、骨與關節感染、肺炎及下呼吸道感等細菌感染。Amikacin完全不經代謝於尿液中排除。而Amoxicillin是半合成青黴素類抗生素，用於治療胃潰瘍、呼吸道、皮膚軟性組織、及泌尿道等細菌感染。45~68% Amoxicillin 會在尿液中排除。本實驗將比較不同定量法在兩種Amikaicn注射製劑產品，Amikin®及Acemycin®；以及Amoxicillin兩種膠囊製劑之產品，Hiconcil®及Amoxicillin®，在健康國人成年男性之生體可用率研究。由血中藥物濃度計算出相關之藥物動力學參數以評估不同定量法的相關性及差異性，及兩組產品是否各具生體相等性。此外，亦收集受試者肌肉注射Amikacin後的尿液,探討Amikacin在尿中排泄。 血漿及尿液檢品中Amikacin濃度之分析，分別以微生物定量法(圓筒平碟法，利用Bacillus subtilis ATCC 6633為分析菌種) ，高效液相層析分析法(利用RP-18層析管柱以氰甲烷:水=39:61以磷酸調至pH 4.5為移動相，UV偵測波長365nm)測定之，及螢光偏極免疫分析法測定。三種分析方法皆有良好的線性關係，其同日、異日精確性及定量極限之變異係數均在10%以內。在不同定量法所得的其它相關之藥物動力學參數，並無統計學上明顯的差異，且相關係數達0.99以上。不同廠牌所得之藥物動力學參數也無統計上之差異。在不同定量法所得的其它相關之藥物動力學參數，並無統計學上明顯的差異。 血漿中 Amoxicillin 濃度之分析分別以微生物定量法(圓筒平碟法，利用Micrococcus luteus ATCC 9341為分析菌種)及高效液相層析分析法(利用RP-18層析管柱以氰甲烷:水=3:97以磷酸調至pH 4.5為移動相。以Acetaminophen為內部標準品，UV偵測波長為228nm)測定之。兩種分析方法也各有良好的線性關係，其同日、異日精確度及定量極限之差異係數均在10%以內，血漿的相對回收率大於90%。在不同定量法所得的其它相關之藥物動力學參數，並無統計學上明顯的差異，且相關係數達0.99以上。不同廠牌所得之藥物動力學參數也無統計上之差異。在不同定量法所得的其它相關之藥物動力學參數，並無統計學上明顯的差異(P>0.05)。; Abstract Amikaicn is a semi-synthetic aminoglycoside antibiotic given by injection. It is used in the treatment of urinary tract infections, septicemia, skin soft tissue infections, bone and joint infections, pneumonia, and lower respiratory tract infections. Amikacin was totally eliminated into urine without metabolizing. Amoxicillin is a semi-synthetic Penicillin, and it is used in several conditions included peptic ulcer, respiratory tract infections, skin soft tissue infections, and urinary tract infections, and there is about 45～68% of amoxicillin excreted into urine. In this study, three quantitative methods for Amikaicn plasma samples and two methods for Amoxicillin plasma samples were evaluated. Also, we collected urine samples from volunteers after the Amikacin administered, intend to observe the excretion of amikacin. We use bioassay (cup-plate method with Bacillus subtilis ATCC 6633 as test organism) 、 high performance liquid chromatography method (RP-18 column, mobile phase is Acetonitrile: water=39:61,pH=4.5, and monitoring at UV 365nm) and fluorescence polarization immunoassay method to analyze the plasma and urine samples after the amikacin administered. These methods showed good linearity, the intra- and inter-day validation and limit of quantification are reasonably with the C.V. values were less than 10%. There was no obviously statistic different in relative parameters from different quantitative methods. The Correlation of different quantitative methods was up to 0.99. Besides, there was no obviously statistic different in relative parameters by different drug products. We use bioassay (cup-plate method with Micrococcus luteus ATCC 9341 as test organism) and high performance liquid chromatography method (RP-18 column, mobile phase is Acetonitrile: Water=3:97,pH 4.5, and monitoring at UV 228nm) to analyze the plasma after the amoxicillin administered. These methods also showed good linearity, the intra- and inter-day validation and limit of quantification are reasonably with the C.V. less than 10%. There was no obviously statistic different in relative parameters from different quantitative methods. The Correlation of two quantitative methods was up to 0.99. Besides, there was no obviously statistic different in relative parameters by the different drug products (P>0.05). |
