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 10(3)/mm3 pre-nephrectomy and 0.9 x 10(3)/mm3 post-nephrectomy, respectively (P = 0.002). The mean lowest recorded platelet counts after melphalan (1 mg/kg) were 115 x 10(3)/mm3 in the pre-nephrectomized dogs, and 9.7 x 10(3/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.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alberts D. S., Chang S. Y., Chen H. S., Evans T. L., Moon T. E. Oral melphalan kinetics. Clin Pharmacol Ther. 1979 Dec;26(6):737–745. doi: 10.1002/cpt1979266737. [DOI] [PubMed] [Google Scholar]
- Alexanian R., Bergsagel D. E., Migliore P. J., Vaughn W. K., Howe C. D. Melphalan therapy for plasma cell myeloma. Blood. 1968 Jan;31(1):1–10. [PubMed] [Google Scholar]
- Chang S. Y., Alberts D. S., Melnick L. R., Walson P. D., Salmon S. E. High-pressure liquid chromatographic analysis of melphalan in plasma. J Pharm Sci. 1978 May;67(5):679–682. doi: 10.1002/jps.2600670529. [DOI] [PubMed] [Google Scholar]
- Furner R. L., Brown R. K., Duncan G. Pharmacokinetics of the absorption, distribution, and elimination of melphalan in the dog. Cancer Treat Rep. 1977 Dec;61(9):1637–1646. [PubMed] [Google Scholar]
- Gierke K. D., Perrier D., Mayersohn M., Marcus F. I. Digoxin disposition kinetics in dogs before and during azotemia. J Pharmacol Exp Ther. 1978 May;205(2):459–464. [PubMed] [Google Scholar]
- SPEED D. E., GALTON D. A., SWAN A. MELPHALAN IN THE TREATMENT OF MYELOMATOSIS. Br Med J. 1964 Jun 27;1(5399):1664–1669. doi: 10.1136/bmj.1.5399.1664. [DOI] [PMC free article] [PubMed] [Google Scholar]