Macromolecular interactions of [14C-ring]melphalan in blood☆

摘要: Abstract The pharmacokinetics and macromolecular interactions of [ 14 C-ring]melphalan ( l -PAM) in blood were studied rats following a single oral dose (20 mg/kg, 0.1 mCi/kg). Radioactivity levels monitored over period 72 hr. highest radioactivity observed at 2 decline from the was biphasic with T 1 α = 7 hr β 75 radioactive species plasma corresponded to unchanged -PAM its two known hydrolytic products 4,2-hydroxyethyl 2-chloroethylamino- -phenylalanine -MOH) 4-[bis(2-hydroxyethyl)amino]- -DOH). In addition, four other major, previously unknown, metabolites detected plasma. At hr, most bound components, 26% macromolecules 62% red cells. Covalent binding cells mainly membrane proteins. Binding hemoglobin soluble components also observed, 5000-fold greater affinity for membranes. These studies suggest extensive interaction melphalan, or metabolites, proteins