體內吸收和溶離度無關之acetaminophen的生體相等性研究   全文下載

Absorption Study with a Dissolution Independent Drug - Acetaminophen

Acetaminophen經研究認為其體內吸收和體外溶解度不相關。本研究報告Acetaminophen國人之藥動力學性質與相對生體可用率之研究報告。以十六個自願健康年輕中國男性的研究對象，經隨意雙盲交叉實驗設計，二次給藥（Scanpharm藥廠及榮民製藥廠之acetaminophen）間隔時間至少相隔一週。給藥500mg後，定時定次探血至12小時。血漿acetaminophen濃度自行改良發展以acetani1id為內標準品，可精確，準確之高壓液相層析定量。Acetaminophen之血漿濃度曲線下面積（AUC∞），最高血漿中濃度（Cmax），到達最高血漿濃度時間（Tmax），排除速率常數，半衰期，口服清除率，均經計算及互相比較。結果顯示二種錠劑無統計上明顯差異。經對數轉換後90%可信區間及power可推論二藥具生體相等性。而比較其在體內吸收及體件溶離度之關係，本研究再次顯示二者無相關性。

Absorption of acetaminophen has been shown to be dissolution independent in human. Both extent and rate of absorption are important variables in the treatment of pain. The absorption of acetaminophen was studied by using two different acetaminophen tablets Depyretin (R)manufactured by Veterans Pharmaceutical Plant, Taiwan, and Scanol (R)manufactured by Scanpharm, Denmark. Both Scanol and Depyretin, each of 500 mg single dose, were administered orally to sixteen healthy young Chinese males with an one-week washout period in a randomized crossover design. Plasma samples used for acetaminophen measurement were taken prior to drug administration and at various times up to 12 hr subsequent to administration. The plasma samples were measured for acetaminophen concentration by an HPLC method. Values for areas under plasma concentration-time curve (extent of absorption), peak plasma concentration, time to peak concentration (rate of absorption), elimination rate constant, elimination half-life and oral clearance were compared for each preparation. Statistical analyses including ANOVA, power analysis and 90% confidence intervals after logarithmic transformation, showed no significant difference in the rate and extent of acetaminophen absorption between Scanol and Depyretin. Furthermore, in vivo absorption did not significantly correlate with in vitro dissolution performance in water. However, differences between these two formulations both in in vitro dissolution and in vivo absorption were not seen. Acetaminophen