Korean J Hematol.  2007 Jun;42(2):122-128. 10.5045/kjh.2007.42.2.122.

Pharmacokinetics of High-dose Intravenous Melphalan in Patients Undergoing Autologous Stem Cell Transplantation

• Lee SY
• Kim JA
• Lee JW
• Koo HJ
• Kim HK

• KMID: 2083509
• DOI: http://doi.org/10.5045/kjh.2007.42.2.122

Abstract

BACKGROUND: Melphalan is frequently used in conditioning regimens prior to autologous stem cell transplantation. The pharmacokinetics of melphalan have shown great interindividual variations. This study aims to investigate the pharmacokinetics of melphalan and to study those influences on renal function and the clinical outcomes.
METHODS
The pharmacokinetics of melphalan following high dose (100~140mg/m(2)) i.v. administration was determined in 11 patients suffering with advanced malignancies and who were undergoing autologous stem cell transplantation. The plasma level of melphalan was assayed by a specific HPLC method.
RESULTS
The pharmacokinetics parameters (median AUC: 625.2mg/L/min, steady-state volume of distribution (Vdss): 14.87L/m(2), total body clearance: 0.2L/min/m(2), half life: 55.9 min, and maximal plasma concentration: 7.61mg/L) were similar to those reported in the literature. No relationship between the pharmacokinetics of melphalan and creatinine clearance, the non-hematologic toxicities and relapse was observed. Only Vdss was correlated with myelosuppression (P<0.05).
CONCLUSION
The pharmacokinetics of melphalan were similar to those reported in Caucasians. The PK parameters did not correlate with the clinical outcomes in patients with normal renal function. Further studies on patients with renal failure are needed.

Keyword

Melphalan; Pharmacokinetics; High dose chemotherapy

MeSH Terms

Area Under Curve
Chromatography, High Pressure Liquid
Creatinine
Half-Life
Humans
Melphalan*
Pharmacokinetics*
Plasma
Recurrence
Renal Insufficiency
Stem Cell Transplantation*
Stem Cells*
Creatinine
Melphalan

Figure

• 

  Fig. 1 Representative profile of concentration-time curve in a patient given intravenous administration of melphalan 140mg/m2.

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