Effect of renal dysfunction in dogs on the disposition and marrow toxicity of melphalan

David S Alberts, H. S G Chen, D. Benz, N. L. Mason

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Abstract

The effect of renal failure on melphalan pharmacology and toxicity has been poorly understood. Such information is of interest because melphalan is the most commonly used anticancer drug in the treatment of multiple myeloma, which is frequently associated with renal failure. We have studied the disposition and marrow toxicity of parenteral melphalan in dogs before and after induction of renal failure with subtotal nephrectomy. The surgical procedure decreased the creatinine clearance by an average of 62% (P=0.001). The lowest neutrophil counts following i.v. melphalan (1 mg/kg) averaged 4.9 x 103/mm:3 pre-nephrectomy and 0.9 x 103/mm3 post-nephrectomy, respectively (P=0.002). The mean lowest recorded platelet counts after melphalan (1 mg/kg) were 115 x 103/mm3 in the pre-nephrectomized dogs, and 9.7 x 103/mm3 in those who had been nephrectomized (P=0.002). Following nephrectomy, i.v. melphalan's terminal-phase plasma half-life and renal clearance were both raised (P=0.02) to 75% over pre-nephrectomy values. These studies show that i.v. melphalan-induced myelosuppression is markedly increased and its plasma elimination and renal clearance significantly decreased in the presence of renal dysfunction in dogs. These data suggest that parenteral melphalan's starting dose be decreased by at least 50% when used in myeloma patients with renal failure.

Original languageEnglish (US)
Pages (from-to)330-334
Number of pages5
JournalBritish Journal of Cancer
Volume43
Issue number3
StatePublished - 1981

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Melphalan
Bone Marrow
Dogs
Kidney
Nephrectomy
Renal Insufficiency
Multiple Myeloma
Platelet Count
Half-Life
Creatinine
Neutrophils
Pharmacology

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Effect of renal dysfunction in dogs on the disposition and marrow toxicity of melphalan. / Alberts, David S; Chen, H. S G; Benz, D.; Mason, N. L.

In: British Journal of Cancer, Vol. 43, No. 3, 1981, p. 330-334.

Research output: Contribution to journalArticle

Alberts, David S ; Chen, H. S G ; Benz, D. ; Mason, N. L. / Effect of renal dysfunction in dogs on the disposition and marrow toxicity of melphalan. In: British Journal of Cancer. 1981 ; Vol. 43, No. 3. pp. 330-334.
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