Sitar D S, Shaw D H, Thirlwell M P, Ruedy J R
Cancer Res. 1977 Nov;37(11):3981-4.
A high-pressure liquid chromatographic method that is used to determine the pharmacokinetic disposition of 5-fluorouracil from the plasma compartment is presented. The method requires only 0.5 ml of plasma for each determination and is sensitive to 0.1 mg of drug per liter. Novel methodology with the use of an ion-specific electrode technique for the determination of urinary excretion kinetics of 5-fluorouracil and its metabolites is also presented. This study demonstrated a much greater variability for the disposition of 5-fluorouracil by cancer patients than has been reported previously. The apparent volume of distribution for this drug varied more than 37-fold. Its plasma half-life varied more than 19-fold, and its urinary excretion half-life varied almost 400-fold. These data are compatible with the hypothesis that this variation could account, at least in part, for the variable therapeutic and toxic response to 5-fluorouracil. The methodology presented in this study is sufficiently simple and sensitive to allow assessment of this hypothesis by investigating cancer patients who receive therapeutic doses of 5-fluorouracil.
本文介绍了一种用于测定血浆中5-氟尿嘧啶药代动力学特征的高效液相色谱法。该方法每次测定仅需0.5毫升血浆，对每升0.1毫克的药物具有敏感性。还介绍了一种使用离子特异性电极技术测定5-氟尿嘧啶及其代谢产物尿排泄动力学的新方法。本研究表明，癌症患者对5-氟尿嘧啶的处置变异性比先前报道的要大得多。该药物的表观分布容积变化超过37倍。其血浆半衰期变化超过19倍，其尿排泄半衰期变化近400倍。这些数据与以下假设相符，即这种变异性至少部分可以解释对5-氟尿嘧啶的治疗和毒性反应的差异。本研究中提出的方法足够简单和灵敏，可通过研究接受治疗剂量5-氟尿嘧啶的癌症患者来评估这一假设。
