Tranchand B, Ploin Y D, Minuit M P, Sapet C, Biron P, Philip T, Ardiet C
Centre Léon Bérard, Lyon, France.
Cancer Chemother Pharmacol. 1989;23(2):95-100. doi: 10.1007/BF00273524.
Previous pharmacokinetic studies of i.v. high-dose melphalan (HDM) have demonstrated large interindividual variations in the pharmacokinetic parameters. We therefore studied the possibility of using a test dose of the drug to determine the level of a subsequent therapeutic dose. This study was undertaken to establish whether the pharmacokinetics of melphalan were linear and reproducible within the same patient and determine whether a linear extrapolation could be carried out from the test dose. The first eight patients were studied on two occasions separated by 2 hours (repeatability stage). Although reasonable evidence for linear pharmacokinetics was obtained from these patients, the data suggested a number of factors that might have introduced errors. Therefore, the second group of ten patients were treated on a slightly different protocol on two occasions 24 h apart (linearity stage). The ratios of the two doses ranged from 1 to 8 (repeatability stage) and from 2.6 to 10 (linearity stage). During both stages there was a good correlation between the AUC measured for the second infusion and that predicted from the first (r = 0.929 and r = 0.943, respectively). We conclude that a test dose can be used to determine the subsequent dose of melphalan necessary to produce a desired AUC.
先前关于静脉注射大剂量美法仑（HDM）的药代动力学研究表明，药代动力学参数存在较大的个体间差异。因此，我们研究了使用该药的试验剂量来确定后续治疗剂量水平的可能性。本研究旨在确定美法仑的药代动力学在同一患者体内是否呈线性且可重复，并确定是否可以从试验剂量进行线性外推。前八名患者分两次进行研究，间隔2小时（重复性阶段）。虽然从这些患者中获得了药代动力学呈线性的合理证据，但数据表明一些因素可能引入了误差。因此，第二组十名患者按照略有不同的方案，在间隔24小时的两次治疗中进行治疗（线性阶段）。两次剂量的比值在1至8之间（重复性阶段），在2.6至10之间（线性阶段）。在两个阶段中，第二次输注测得的AUC与第一次预测的AUC之间均具有良好的相关性（分别为r = 0.929和r = 0.943）。我们得出结论，试验剂量可用于确定产生所需AUC所需的后续美法仑剂量。
