Bosanquet A G, Gilby E D
Cancer Chemother Pharmacol. 1984;12(3):183-6. doi: 10.1007/BF00256542.
Melphalan absorption was studied over three consecutive days in five patients with multiple myeloma. On 1 day melphalan (approximately 7 mg/m2 = 10-12 mg) was administered IV, on 1 day PO fasting, and on 1 day PO after a standard breakfast. The order was different for each patient to minimise trends that might affect absorption. Melphalan concentrations were determined by high-pressure liquid chromatography and fitted to biexponential equations by computer. The parameters of these equations were in broad agreement with previously published data, and melphalan absorption varied between patients. Considerable differences were observed in the melphalan concentration curves between the 'PO fed' and 'PO fasting' days: on the PO fed days the delay before absorption started was longer (1.1 +/- 0.5 h as against 0.3 +/- 0.1 h); peak plasma levels were one-third the value (65 +/- 15 ng/ml; 195 +/- 80 ng/ml) and occurred at twice the time after administration (2.8 +/- 0.8 h; 1.3 +/- 0.3 h); and areas under the curve were smaller 10.8 +/- 4.7 min X micrograms/ml; 23.8 +/- 13.8 min X micrograms/ml). There was a significant difference between the fraction of the dose of melphalan absorbed on the PO fed day (0.49 +/- 0.20) and on the PO fasting day (0.93 +/- 0.22), with P less than 0.005. This work suggests that melphalan should be taken first thing in the morning to obtain greatest absorption.
在5例多发性骨髓瘤患者中，连续3天研究了美法仑的吸收情况。在1天静脉注射美法仑（约7mg/m² = 10 - 12mg），在1天空腹口服，在1天标准早餐后口服。每位患者的给药顺序不同，以尽量减少可能影响吸收的趋势。通过高压液相色谱法测定美法仑浓度，并通过计算机将其拟合为双指数方程。这些方程的参数与先前发表的数据大致一致，且美法仑的吸收在患者之间存在差异。在“餐后口服”和“空腹口服”日的美法仑浓度曲线之间观察到相当大的差异：在餐后口服日，吸收开始前的延迟更长（1.1±0.5小时，而空腹口服日为0.3±0.1小时）；血浆峰值水平为空腹口服日的三分之一（65±15ng/ml；195±80ng/ml），且在给药后出现的时间为空腹口服日的两倍（2.8±0.8小时；1.3±0.3小时）；曲线下面积更小（10.8±4.7分钟×微克/毫升；23.8±13.8分钟×微克/毫升）。餐后口服日和美法仑空腹口服日吸收的美法仑剂量分数之间存在显著差异（0.49±0.20和0.93±0.22），P值小于0.005。这项研究表明，美法仑应在早晨第一件事时服用以获得最大吸收。
