Pharmacokinetics of high-dose melphalan in adults: influence of renal function.

BACKGROUND

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).

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 (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.

CONCLUSIONS

Renal insufficiency did not lead to a large decrease in melphalan clearance compared to interindividual variations in systemic clearance.