Cunningham D, Cummings J, Blackie R B, McTaggart L, Banham S W, Kaye S B, Soukop M
Department of Medical Oncology, Glasgow Royal Infirmary, U.K.
Med Oncol Tumor Pharmacother. 1988;5(2):117-23. doi: 10.1007/BF02985449.
We have studied the pharmacokinetics of single agent high dose cyclophosphamide (HDC) (160-240 mg kg-1) given as repeated intravenous (i.v.) infusions to six patients with small cell lung cancer (SCLC), and HDC (180 mg kg-1) combined with etoposide (750-1000 mg m-2) as repeated i.v. infusions to five patients with SCLC and two patients with teratoma. HDC has a similar pharmacokinetic profile to low dose cyclophosphamide, with a half-life of 4.83 +/- 1.3 h. Repeated administration of HDC produced a small but significant shortening of the half life (P = 0.02). The terminal half-life of high dose etoposide was 7.7 +/- 2 h which is similar to our previous results with low dose etoposide (50-300 mg m-2), but the volume of distribution which was 35.5 +/- 11.6 1. was significantly increased (P less than 0.001). Plasma steady state concentrations of 26.2 +/- 11.7 micrograms ml-1 were achieved. The possible mechanism for the alteration of volume of distribution of etoposide will be discussed.
我们研究了对6例小细胞肺癌（SCLC）患者重复静脉输注单药高剂量环磷酰胺（HDC）（160 - 240 mg kg-1）的药代动力学，以及对5例SCLC患者和2例畸胎瘤患者重复静脉输注HDC（180 mg kg-1）联合依托泊苷（750 - 1000 mg m-2）的药代动力学。HDC的药代动力学特征与低剂量环磷酰胺相似，半衰期为4.83±1.3小时。重复给予HDC导致半衰期略有但显著缩短（P = 0.02）。高剂量依托泊苷的终末半衰期为7.7±2小时，这与我们之前使用低剂量依托泊苷（50 - 300 mg m-2）的结果相似，但分布容积为35.5±11.6 1，显著增加（P＜0.001）。血浆稳态浓度达到26.2±11.7微克/毫升。将讨论依托泊苷分布容积改变的可能机制。
