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Kinetics of intravenous melphalan
Author(s) -
Alberts David S.,
Chang Sai Y.,
Chen H.-S. George,
Moon Thomas E.,
Evans Thomas L.,
Furner Raymond L.,
Himmelstein Kenneth,
Gross Joseph F.
Publication year - 1979
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt197926173
Subject(s) - melphalan , chemistry , pharmacokinetics , urine , pharmacology , chromatography , in vivo , drug , half life , urinary system , intravenous infusions , medicine , chemotherapy , biochemistry , biology , microbiology and biotechnology
We have studied the disposition and elimination of melphalan after intravenous administration in 9 patients with cancer. High‐pressure liquid chromatography and 14 C‐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 14 C 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.