本研究旨在檢討國產norfloxacin製劑Gentle®與一標準對照品Baccidal®在國人受試者體內動態學上之異同，並比較其是否具有生物相等性。共有八位成年健康男性參與本研究，依平衡二向交叉實驗設計(two-way crossover design)，每次依禁食過夜經口投予400mg norfloxacin，並於0.05，1.0，2.0，4.0，8.0，12.0及24.0小時抽血，血清中藥品濃度以HPLC方法定量，所得數據以本研究室開發之KMCP軟體以單室模式求出藥物動態學之各項參數。
結果顯示Gentle®及Baccidal®之Cmax分別為0.96±0.089及0.99±0.110μg/ml；Tmax皆為2.0±0.0 hr；Kel值分別為0.1101±0.006及0.098±0.005hr-1；T1/2、β分別為6.909±0.483及7.094±0.350hr；Ka值分別為2.444±0.118及2.490±0.096hr-1；T1/2、α分別為0.278±0.019及0.277±0.010hr；AUC0∞則分別為9.183±1.257及9.550±1.300μg.hr/ml。
各參數值以ANOVA進行檢定，兩種製劑之間均未有顯著差異(P>0.05)。此外，各參數平均值差百分筆均小於20%，且在基於α=0.05及1－β=0.8之時，求得之最小檢出差delta值均小於0.2。另以ANOVA求得之MES值，估計95%信賴區間後，各參數值之平均差皆落於其區間內。在計算檢出力(1－β)後發現，除Kel及T1/2、β小於0.8外，其餘各參數值皆大於0.8。綜合試驗結果，並無證據顯示兩者在藥劑學上，動態學上與治療效能上有所不同。 The pharmacokinetics and bioequivalence of two norfloxacin, Gentle® capsule and Baccidal® tablet, were compared in eight healthy male volunteers. A 400 mg dose of norfloxacin was given orally after an overnight fasting to volunteers in a balanced two-way cross-over study. Blood samples were obtained at 0.05，1.0，2.0，4.0，8.0，12.0 and 24.0 hours after the dosing. Nor-floxacin concentration in serum was assayed by a high pressure liquid chromatographic method using an UV detector. All the data was processed by KMCP computer software and the pharmacokinetic parameters were calculated, based on one-compartment model. The results revealed that the maximal con---centration (Cmax) of Gentle® and Baccidal® was 0.96 ± 0.089 and 0.99 ± 0.110;the time to reach maximal concentration (Tmax) was 2.0 ± 0.0 for both; the elimination constant (Kel) was O.101 ± O.006 and 0.098±0.005 hr-l ; the elimination half life (T1/2、β) was 6.909±0.483 and 7.094±0.350 hr; the absorption constant (Ka) was 2.444±0.188 and 2.490±0.096 hr-l ; the absorption half life (T1/2、α) was 0.278±0.019 and 0.277 ± 0.010 hr: the area under curve (from 0 to 12 hours) (AUC 0-12) was 7.106 ± 1.065 and 7.380 ± 1.044 μg.hr/ml; and the area under curve (from 0 hour to infinity) (AUC 0-∞) was 9.183 ± I.257 and 9.550 ± 1.300 μg.hr/ml respectively. There were no significant difference found between the two groups after statistical analysis with two-way groups after statistical analysis with two-way ANOVA (p > 0.05). A series of statistical parameters including d%. delta, and 95% C.I. were calculated by, a bioequivalence test computer software of Yamaoka Simi. In order to Strengthen the statistical evidence, the power of the test (1－β) was also calculated. After evaluating all the parameters, there was no significant difference found between the two groups. Therefore, the high sinlilarity of these two formulations is suggested by the authors.
關聯:
嘉南學報 16期 : 頁A85-A94 轉載 The Kaohsiung Journal of Medical Sciences 6(9) : p.501-510 (1990)
