Pinguet F, Martel P, Fabbro M, Petit I, Canal P, Culine S, Astre C, Bressolle F
Laboratoire d'Onco-Pharmacologie, Centre Régional de Lutte contre le Cancer, Montpellier, France.
Anticancer Res. 1997 Jan-Feb;17(1B):605-11.
The pharmacokinetics of melphalan following high-dose (140 mg/m2) i.v. administration were determined in 20 patients with advanced malignancies undergoing peripheral blood hematopoietic progenitor-cell transplantation. Melphalan was assayed in plasma by a specific HPLC method with UV detection. Plasma levels of melphalan declined in a biexponential fashion with a mean terminal half-life of 83 minutes (range 52-168 minutes). Estimated peak plasma concentrations ranged from 1.65 to 14.5 micrograms/ml. Plasma levels were lower than the limit of quantitation of the method used (20 ng/ml) 24 hours after drug administration. The average volume of distribution and total clearance were 317 ml/min/m2 (range 127-797 ml/min/m2) and 37.9 l/m2 (range 15.4-108 l/m2), respectively. These parameters are similar to those reported in the literature. A weak correlation was found between total clearance of melphalan and creatinine clearance (p < 0.05). No relationship between the pharmacokinetics of melphalan and myelosuppression and non-hematologic toxicities was recovered. This pharmacokinetic study indicates that on the assumption that there is no more circulating melphalan after seven elimination half-lives, it may be possible to reinfuse autologous PBPC 10-20 hours after melphalan administration.
在20例接受外周血造血祖细胞移植的晚期恶性肿瘤患者中，测定了大剂量（140mg/m²）静脉注射美法仑后的药代动力学。采用具有紫外检测的特定高效液相色谱法测定血浆中美法仑的含量。美法仑的血浆水平呈双指数下降，平均终末半衰期为83分钟（范围52 - 168分钟）。估计的血浆峰浓度范围为1.65至14.5μg/ml。给药24小时后，血浆水平低于所用方法的定量限（20ng/ml）。平均分布容积和总清除率分别为317ml/min/m²（范围127 - 797ml/min/m²）和37.9l/m²（范围15.4 - 108l/m²）。这些参数与文献报道的相似。发现美法仑的总清除率与肌酐清除率之间存在弱相关性（p < 0.05）。未发现美法仑的药代动力学与骨髓抑制和非血液学毒性之间存在关联。这项药代动力学研究表明，假设在七个消除半衰期后不再有循环的美法仑，那么在美法仑给药后10 - 20小时回输自体外周血祖细胞可能是可行的。
