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).


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.
Kergueris
M F
MF
Laboratoire de Pharmacologie Clinique, ICERC, CHU, Nantes, France.
Milpied
N
N
Moreau
P
P
Harousseau
J L
JL
Larousse
C
C
D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000378:metabolism; D000704:Analysis of Variance; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D012984:Software
D003404:Creatinine; D008558:Melphalan