Kinetics of intravenous melphalan

Abstract

We have studied the disposition and elimination of melphalan after intravenous administration in 9 patients with cancer. High-pressure liquid chromatography and ¹⁴C-melphalan were used to assay drug concentration in plasma and urine. Composite plasma t½β was 7.7 ± 3.3 and t½β was 108 ± 20.8 min for 8 of the patients. The mean 24-hr urinary excretion of melphalan was 13.0 ± 5.4% of the administered dose. In 2 patients, 80% to 100% of the measured ¹⁴C counts in plasma and urine samples at each study interval, up to 24 hr after drug administration, could be accounted for by the sum of parent compound, monohydroxy and dihydroxy products, and methanol nonextractable radioactivity (i.e., protein-bound activity). These data and evidence of rapid disappearance from plasma at 37° in vitro suggest that spontaneous degradation, and not enzymatic metabolism, is the major determinant of the t½β of melphalan in vivo.