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Pharmacokinetics of oral melphalan in relation to renal function in multiple myeloma patients
Affiliation:1. Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota;2. Masonic Cancer Center Biostatistics Core, University of Minnesota, Minneapolis, Minnesota;3. Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota;4. Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, Minnesota;1. Hematology and Transplantation, Saint Louis Hospital, Paris, France;2. Cellular Biology, Saint Louis Hospital, Paris, France;3. University of Paris, INSERM U1131, Paris, France;4. Clinical Investigation Center, Saint Louis Hospital, Paris, France;5. Adult Hematology Unit, Saint Louis Hospital, Paris, France;6. Hematology Central Laboratory, Saint Louis Hospital, Paris, France;7. University of Paris, INSERM U976, Paris, France;8. Hematology Senior Unit, Saint Louis Hospital, Paris, France;9. University of Paris, INSERM U944, Paris, France
Abstract:
The impact of renal function on oral melphalan pharmacokinetics was studied in 15 patients with multiple myeloma. A two-fold interindividual variation in the plasma concentration-time curve (AUC) was found. An increase in AUC and melphalan mean residence time (MRT) was noted in patients with renal dysfunction. No correlation was found between GFR and the terminal plasma half-life time. We conclude from these results that renal dysfunction is associated with an increase in AUC and MRT of oral melphalan. A careful follow-up of hematological toxicity and possibly a dose reduction of melphalan are proposed for myeloma patients with renal impairment.
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