De Bruijn E A, Slee P H, Van Oosterom A T, Lameijer D W, Roozendaal K J, Tjaden U R
Laboratory of Cancer Research & Clinical Oncology, University of Antwerp, Belgium.
Pharm Weekbl Sci. 1988 Oct 14;10(5):200-6. doi: 10.1007/BF01956871.
Cyclophosphamide was administered to 12 breast cancer patients in combination with methotrexate and fluorouracil. Doses prescribed were cyclophosphamide 75 mg/m2, methotrexate 30 mg/m2 and fluorouracil 500 mg/m2 (per square meter body surface). Cyclophosphamide was administered intravenously and orally in aqueous solutions and in tablets in a randomized cross-over trial. Methotrexate and fluorouracil were administered intravenously, methotrexate was given first and then fluorouracil. Assays of cyclophosphamide in blood plasma were performed by capillary gas chromatography. Data of mean bioavailability of cyclophosphamide administered by tablets were suggestive of sufficient absorption. In 2 patients, however, a lower bioavailability of cyclophosphamide was demonstrated. Intra-individual differences in the terminal slope of the plasma decay curves after intravenous and oral administration in some patients decreased the calculated bioavailability of cyclophosphamide, if these values were included in the calculation of cyclophosphamide bioavailability. Compared with the administration of the solutions peak times, lag-times and mean absorption times of cyclophosphamide given in tablets were markedly prolonged. It is concluded that interactions between cyclophosphamide and methotrexate and/or fluorouracil after oral dosing as tablets are different from interactions observed after intravenous administration of cyclosphosphamide.
环磷酰胺与甲氨蝶呤和氟尿嘧啶联合应用于12例乳腺癌患者。规定剂量为环磷酰胺75mg/m²、甲氨蝶呤30mg/m²和氟尿嘧啶500mg/m²（每平方米体表面积）。在一项随机交叉试验中，环磷酰胺以水溶液和片剂形式静脉内和口服给药。甲氨蝶呤和氟尿嘧啶静脉内给药，先给予甲氨蝶呤，然后给予氟尿嘧啶。采用毛细管气相色谱法测定血浆中环磷酰胺的含量。片剂给药的环磷酰胺平均生物利用度数据表明吸收充分。然而，有2例患者环磷酰胺的生物利用度较低。如果将某些患者静脉内和口服给药后血浆衰减曲线的终末斜率的个体内差异纳入环磷酰胺生物利用度的计算中，则会降低环磷酰胺的计算生物利用度。与溶液给药相比，片剂给药的环磷酰胺的达峰时间、滞后时间和平均吸收时间明显延长。得出的结论是，口服片剂形式的环磷酰胺与甲氨蝶呤和/或氟尿嘧啶之间的相互作用与静脉内给予环磷酰胺后观察到的相互作用不同。
