Wagner T, Heydrich D
Arzneimittelforschung. 1982;32(5):566-8.
Levels of cyclophosphamide (CP, Endoxan) and metabolites were determined in blood and pleural effusions of 5 cancer patients receiving 20 mg/kg CP i.v. The pleural concentrations of CP and its stable deactivated metabolites as 4-keto-CP and carboxyphosphamide increased slowly and even after 4 to 6 an equilibrium with plasma levels was not achieved completely. Plasma peak levels of activated CP (4-hydroxy-CP + aldophosphamide) determined after conversion into the stable derivative 4-(S-benzyl)sulfido-CP or by a fluorometric test were in the range of 1 to 2 nmol/ml. Using these techniques, as two independent methods, amounts of activated CP in pleural effusion were found to be below the limit of detection (0.1-0.2 nmol/ml). Also the alkylating rates of proteins in the pleural effusions were only 20% of those measured in blood samples. The relatively short plasma half-life (approx. 15 min) of 4-hydroxy-CP, when compared with the slow passage of CP-metabolites from blood to the pleural space, is assumed to be the reason for the failure of detection of activated CP and low levels of alkylating material observed in the pleural effusions.
测定了5例接受20mg/kg静脉注射环磷酰胺（CP，癌得星）的癌症患者血液和胸腔积液中环磷酰胺及其代谢产物的水平。CP及其稳定的失活代谢产物如4-酮基-CP和羧基磷酰胺在胸腔中的浓度上升缓慢，甚至在4至6小时后仍未完全与血浆水平达到平衡。转化为稳定衍生物4-（S-苄基）硫代-CP后或通过荧光测定法测定的活性CP（4-羟基-CP + 醛磷酰胺）的血浆峰值水平在1至2nmol/ml范围内。使用这两种独立的技术方法，发现胸腔积液中活性CP的含量低于检测限（0.1 - 0.2nmol/ml）。胸腔积液中蛋白质的烷基化率也仅为血液样本中测量值的20%。与CP代谢产物从血液缓慢进入胸腔相比，4-羟基-CP相对较短的血浆半衰期（约15分钟）被认为是胸腔积液中活性CP检测失败以及烷基化物质水平较低的原因。
