We have studied the disposition and elimination of melphalan after intravenous administration in 9 patients with cancer. High-pressure liquid chromatography anti 14C-melphalan were used to assay drug concentration in plasma and urine. Composite plasma t 1 2α was 7.7 ± 3.3 and t 1 2β 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 non extractable 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 t 1 2 of melphalan in vivo.
ASJC Scopus subject areas
- Pharmacology (medical)