Alkeran Mechanism of Action

Pharmacology: Pharmacodynamics: Melphalan is a bifunctional alkylating agent. Formation of carbonium intermediates from each of the 2 bis-2-chloroethyl groups enables alkylation through covalent binding with the 7-nitrogen of guanine on DNA, cross-linking 2 DNA strands and thereby preventing cell replication.
Pharmacokinetics: The absorption of melphalan was found to be highly variable in 13 patients given 0.6 mg/kg body weight orally, with respect to both the time to 1st appearance of melphalan in the plasma (range 0-336 min) and the peak plasma concentration (range 70-630 ng/mL). In 5 of the patients who were given an equivalent IV dose, the mean absolute bioavailability of melphalan was found to be 56±27%. The plasma mean terminal elimination half-life was 90±57 min with 11% of melphalan being recovered in the urine over 24 hrs.
In a study of 18 patients administered melphalan 0.2-0.25 mg/kg body weight orally, maximum plasma concentration (range 87-350 ng/mL) was reached within 0.5-2 hrs. The mean elimination half-life was 1.12±0.15 hrs. The administration of Alkeran immediately after food delayed the time to achieving peak plasma concentrations and reduced the area under the plasma concentration-time curves by between 39% and 45%. Toxicology: Preclinical Safety Data: Melphalan is mutagenic in animals.