Pharmacokinetic Properties and Relative Bioavailability of Acetaminophen Tablets

Acetaminophen錠劑之藥物動力學與其相對生體可用率之研究

胡幼圃(Oliver Yoa-Pu Hu) ； 鮑力恆(Li-Heng Pao) ； 何善台(Shang-Tai Ho) ； 王志中(Jhi-Joung Wang) ； 李宇萍(Yu-Ping Lee) ； 詹素妃(Shu-Fei Chan) ； 賴金星(Jin-Shing Lai) ； 李正華(Cheng-Hua Lee) ； 鍾柄泓(Ping-Hong Chung)

《Journal of Medical Sciences》 11卷4期 (1991/08) Pp. 281-295

摘要

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結果。以十二個自願健康年輕中國男性為研究對象，經隨意雙盲交叉試驗設計，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500 mg後，定時定次採血集尿分別至24至48小時。血漿及尿中acetaminophen濃度由自行改良發展以acetanilid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，腎清除率及Acetaminophen於尿中排除之百分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。Acetaminophen之腎清除率會受尿流速與尿pH值的影響。特別是受尿pH的影響，尚未有文獻報導。此發現可能應用在Acetaminophen中毒時之解毒。當比較中國人與文獻中記載西方人之Acetaminophen藥物動力學參數，中國人有較大之口服清除率，腎清除率，較大分佈體積與較長之排除半衰期。由此可推中國人可能比西方人需較大之Acetaminophen劑量來達最低有效濃度。

關鍵字

Acetaminophen錠劑 ； 相對生體可用率 ； 藥物動力學

並列摘要

The pharmacokinetic properties and relative bioavailability of two different acetaminophen tablets Depyretin®, manufactured by Veterans Pharmaceutical Plant, Taiwan, and Scanol®, manufactured by Scanpharm, Denmark, were conducted. Both Scanol and Depyretin, each of 500 mg, were administered orally to twelve healthy young Chinese males at an interval of one week in a randomized crossover design. The plasma samples for acetaminophen measurement were taken before drug administration and at various times up to 12 hr following administration. The plasma samples were measured for acetaminophen concentration by the HPLC method. Values for area under the plasma concentration-time curve, elimination rate constant, half-life, peak plasma concentration, time to peak concentration, oral clearance, renal clearance and percentage of drug excreted in urine were compared for each preparation. No pharmacokinetic and clinical differences were found between the acetaminophen products Scanol and Depyretin. In other words, there is no evidence that these two preparations are not bioequivalent. Acetaminophen renal clearance was dependent on urinary flow rate and urinary pH value. These findings may be applied in the case of clinical detoxification of acetaminophen overdose. After comparing published acetaminophen pharmacokinetic properties in healthy Casian volunteers with those in Chinese, greater oral and renal clearance, (21.61 ± 8.33 ml/min vs. 13 ml/min), larger volume of distribution and longer elimination half-life were observed in Chinese. Therefore, larger acetaminophen dosage may be needed for Chinese to reach minimum effective concentration.

並列關鍵字

Acetaminophen tablets ； Relative Bioavailability ； Pharmacokinetics