Pharmacokinetics of high-dose melphalan in adults: influence of renal function
Kergueris, M.F.; Milpied, N.; Moreau, P.; Harousseau, J.L.; Larousse, C.
Anticancer Research 14(6a): 2379-2382
1994
ISSN/ISBN: 0250-7005 PMID: 7825976 Document Number: 1116
Background: The pharmacokinetics of melphalan were studied in 20 patients with multiple myeloma, primary amyloidosis or lymphoma after IV dose of 140 mg/m-2 infused over 30 minutes (two patients were treated with a higher dose). Materials and Methods: 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. Results: Pharmacokinetic parameters (CI-T, V-dss, t-1/2) and areas under the curve (AUC) were comparable to those obtained by Ardiet et al. after rapid IV injection. For all patients, AUC, CI-T, V-dss, t-1/2beta and MRT were significantly correlated with creatinine clearance; the different pharmacokinetic parameters calculated showed great interindividual variations. Conclusions: Renal insufficiency did not lead to a large decrease in melphalan clearance compared to interindividual variations in systemic clearance.
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