Ceftriaxone經肌肉內注射之體內動態與生物相等性研究   全文下載

Comparative Study on the Pharmacokinetic Bioequivalence of Two Intravascular Ceftriaxone Preparations

本研究係以兩種Ceftriaxone注射劑，即“ 汎生”舒復肌肉注射劑（Cefin(R) for I.M. injection“ Panbiotic”，臺灣汎生製藥廠製）與“羅氏”羅氏芬（Rocephin(R)“ Roche”赫夫門羅氏藥廠製），以十二位健康男性自願者，經肌肉內注射1公克的Ceftriaxone disodium hemiheptahydrate，並以雙向交叉檢定方法，研究此二注射劑在體內之動態與其生物相等性；受試者之血液檢品取自十二位受試者注射藥品０，0.25，0.5，0.75，1.0，1.5，2.0，2.5，3.0，4.0，6.0，8.0，10.0，12.0，24.0小時後之靜脈血液。血漿中的ceftriaxone濃度則以高效液相層析法，紫外光檢測器檢測。所有資料處理，以SigmaPlot及SigmaStat電腦軟體。基於一室式模式計算出藥品動態參數。結果顯示Cefin(R)及Rocephin(R)的最高血中濃度（Cmax）分別為118.89 ± 15.59 及120.02 ± 15.04μg／ml；達最高血中濃度時間分別為（Tmax） 1.83 ± 0.33 及1. 75 ± 0.26 小時；廓清常數（Ke）兩者皆為0.11 ± 0.02 hr-1；廓清半生期（T1／2，s） 是6.54 ± 0.93及6.25 ± 0.90 hr-1；吸收常數（Ka）各為1. 83 ± 0.38 及1. 81 ± 0.28 hr-1；曲線下面積（從0至t小時）（AUC0- t）分別為1263.45 ± 106.69及1218.86 ± 118.30μg.hr／ml；曲線下面積（從0至無窮）（AUC0-∞）為1405.97 ± 138.87 及1356.27 ± 166.90μg.hr／ml；Cl／F分別為0.71 ± 0.07 及0.75 ± 0.09 L／hr；Vd s 各別為8.49 ± 1.21及8.11 ± 1.17 L。此等數據更進一步經過檢定力試驗（Power test） （1-s）。依據Ceftriaxone經肌肉內注射後，在本研究之體內動態參數及其統計強度值，以及自然對數轉換的Cmax及AUC，可證明此兩種注射劑具有生體相等性。 The pharmacokinetics and bioequivalence of two Ceftriaxone preparations, CefinR 'Panbiotic' for I.M injection and RocephinR 'Roche', were compared in twelve healthy male volunteers. A 1g dose of Ceftriaxone disodium hemiheptahydrate was given intramuscularly in a balanced two-way cross-over study for CefinR and RocephinR groups. Blood samples were obtained at 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0 and 24.0 hours after the dosing. Ceftriaxone concentration in plasma was assayed by a high performance liquid chromatographic method using an UV detector. All the data was processed by SigmaPlotR and SigmaStatR computer software and the pharmacokinetic parameters were calculated, based on one-compartment model. The results revealed that the maximal concentration (Cmax) of CefinR and RocephinR was 118.89± 15.59 and 120.02± 15.04 μg/ml; the time to reach maximal concentration (Tmax) was 1.83 ± 0.33 and 1.75 ± 0.26 hr ; the elimination rate constant (Ke) was 0.11 ± 0.02 hr-1 for both ; the elimination half life (T 1/2, β) was 6.54 ± 0.93 and 6.25 ± 0.90 hr ; the absorption rate constant (Ka) was 1.83±0.38 and 1.81 ±0.28 hr1; the area under curve (from 0 to t hou-rs) (AUC0-t) was 1263.45 ± 106.69 and 1218.86± 118.30 μg hr/ml ; the area under curve ( from 0 hour to infinity) (AUC0-∞) was 1405.97 ± 138.87 and 1356.27 ± 166.90 μg hr/ml ; Cl/F was 0.71 ± 0.07 and 0.75±0.09 (L/hr); Vdβwas 8.49± 1.21 and 8.11 ± 1.17(L), respectively. In order to strengthen the statistical evidence, the power of the test ( 1-β) was also calculated. According to the statically pharmacokinetic results, statistical power value, and the natural logarithmic transformation of Cmax and AUC, we conclude that CefinR manufactured by Panbiotic and RocephinR manufactured by Roche are bioequivalent."

The pharmacokinetics and bioequivalence of two Ceftriaxone preparations, CefinR 'Panbiotic' for I.M injection and RocephinR 'Roche', were compared in twelve healthy male volunteers. A 1g dose of Ceftriaxone disodium hemiheptahydrate was given intramuscularly in a balanced two-way cross-over study for CefinR and RocephinR groups. Blood samples were obtained at 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0 and 24.0 hours after the dosing. Ceftriaxone concentration in plasma was assayed by a high performance liquid chromatographic method using an UV detector. All the data was processed by SigmaPlotR and SigmaStatR computer software and the pharmacokinetic parameters were calculated, based on one-compartment model. The results revealed that the maximal concentration (Cmax) of CefinR and RocephinR was 118.89± 15.59 and 120.02± 15.04 µg/ml; the time to reach maximal concentration (Tmax) was 1.83 ± 0.33 and 1.75 ± 0.26 hr ; the elimination rate constant (Ke) was 0.11 ± 0.02 hr-1 for both ; the elimination half life (T 1/2, β) was 6.54 ± 0.93 and 6.25 ± 0.90 hr ; the absorption rate constant (Ka) was 1.83±0.38 and 1.81 ±0.28 hr1; the area under curve (from 0 to t hou-rs) (AUC0-t) was 1263.45 ± 106.69 and 1218.86± 118.30 µg hr/ml ; the area under curve ( from 0 hour to infinity) (AUC0-∞) was 1405.97 ± 138.87 and 1356.27 ± 166.90 µg hr/ml ; Cl/F was 0.71 ± 0.07 and 0.75±0.09 (L/hr); Vdβwas 8.49± 1.21 and 8.11 ± 1.17(L), respectively. In order to strengthen the statistical evidence, the power of the test ( 1-β) was also calculated. According to the statically pharmacokinetic results, statistical power value, and the natural logarithmic transformation of Cmax and AUC, we conclude that CefinR manufactured by Panbiotic and RocephinR manufactured by Roche are bioequivalent.