Kergueris M F, Milpied N, Moreau P, Harousseau J L, Larousse C
Laboratoire de Pharmacologie Clinique, ICERC, CHU, Nantes, France.
Anticancer Res. 1994 Nov-Dec;14(6A):2379-82.
The pharmacokinetics of melphalan were studied in 20 patients with multiple myeloma, primary amyloidosis or lymphoma after IV dose of 140 mg/m2 infused over 30 minutes (two patients were treated with a higher dose).
Six patients received melphalan alone, 8 received melphalan combined with total body irradiation, 2 received busulphan plus melphalan and 4 received the BEAM association (BCNU + etoposide + high dose aracytine + high dose melphalan). Creatinine clearance was measured immediately before the infusion of melphalan, and 9 blood samples were taken to monitor elimination kinetics.
Pharmacokinetic parameters (CIT, Vdss, t1/2) and areas under the curve (AUC) were comparable to those obtained by Ardiet et al after rapid IV injection. For all patients, AUC, CIT, Vdss, t1/2 beta and MRT were significantly correlated with creatinine clearance; the different pharmacokinetic parameters calculated showed great interindividual variations.
Renal insufficiency did not lead to a large decrease in melphalan clearance compared to interindividual variations in systemic clearance.
对20例患有多发性骨髓瘤、原发性淀粉样变性或淋巴瘤的患者静脉注射140mg/m²美法仑，输注时间为30分钟（2例患者接受了更高剂量的治疗），研究了美法仑的药代动力学。
6例患者单独接受美法仑治疗，8例患者接受美法仑联合全身照射，2例患者接受白消安加美法仑治疗，4例患者接受BEAM方案（卡莫司汀+依托泊苷+大剂量阿糖胞苷+大剂量美法仑）。在输注美法仑前立即测量肌酐清除率，并采集9份血样以监测消除动力学。
药代动力学参数（CIT、Vdss、t1/2）和曲线下面积（AUC）与Ardiet等人快速静脉注射后获得的结果相当。对于所有患者，AUC、CIT、Vdss、t1/2β和MRT与肌酐清除率显著相关；计算出的不同药代动力学参数显示出很大的个体差异。
与全身清除率的个体差异相比，肾功能不全并未导致美法仑清除率大幅下降。
