兩種不同處方錠劑Simvastatin於台灣受試者之生體相等性研究   全文下載

Bioequivalence Assessment of Two Simvastatin Tablets in Healthy Taiwanese Volunteers

本研究旨在評估兩種simvastatin錠劑（Zolotin及ZOCORR）於26位台灣男性健康受試者之生體相等性研究。利用隨機，二個次序，二週期，交叉之試驗設計方式單劑量口服投與simvastatin錠劑。分別於投藥前及投藥後第0.25、0.5、0.75、1、1.5、2、2.5、3、3.5、4、5、6、8、10、12、14及24hr，收集血液檢品，透過液相層析串聯質譜儀（LC/MS/MS）分析其中β-hydroxyacid simvastatin之濃度。以非房室模式分析藥動學參數，且經用對數轉換過之AUC0-t，AUC0-∞，AUC0-max作變異數分析。Zolotin與ZOCORR的Cmax分別為4.78 ± 2.75及4.52 ± 2.01ng/mL，Tmax為3.80 ± 1.63及4.31 ± 1.73 hr，T1/2為4.32 ± 1.82及5.11 ± 2.49hr，AUC0-t為35.6 ± 21.7及36.5 ±20.0 ng×hr/mL，AUC0-∞為38.1 ± 24.3及40.3 ± 23.6 ng×hr/mL。二種錠劑之血中β-hydroxyacid simvastatin之ln（AUC0-t），ln（AUC0-∞）及ln（Cmax）的90%均在可信賴度區間介於80%至125%間，符合生體相等性規範。根據以上結果，可證明此學名藥品Zolotin和ZOCORR具生體相等性。

The pharmacokinetics and bioequivalence of two tablets of simvastatin, Zolotin and ZOCOR®, were evaluated in 26 healthy male Taiwanese volunteers who reside in Taiwan. The experiments were designed as a randomized, two-sequence, two-period and single-dose crossover study. Blood samples were obtained at 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 14 and 24 hr after oral dosing of one tablet. β-hydroxyacid simvastatin concentrations in plasma were analyzed by a validated LC/MS/ MS method. The pharmacokinetic parameters were analyzed by non-compartmental analysis. The analysis of variance was carried out using log-transformed AUC0-t, AUC0-∞ and Cmax. The results revealed that the Cmax of Zolotin and ZOCOR® were 4.78 ± 2.75 ng/mL and 4.52 ± 2.01 ng/mL; the Tmax were 3.80 ± 1.63 hr and 4.31 ± 1.73 hr; the T1/2 were 4.32 ± 1.82 hr and 5.11 ± 2.49 hr; the AUC0-t were 35.6 ± 21.7 ng×hr/mL and 36.5 ± 20.0 ng×hr/mL; and the AUC0-∞ were 38.1 ± 24.3 ng×hr /mL and 40.3 ± 23.6 ng×hr/mL, respectively. The ratios of log-transformed AUC0-t, AUC0-∞, and Cmax values of the plasma β-hydroxyacid simvastatin between two tablets were within the range of 80-125% as judged by 90% confidence intervals and satisfied the bioequivalence criteria. The generic simvastatin tablets formulation, Zolotin, was shown to be bioequivalent to the ZOCOR® tablets.