Pharmacokinetics of peptichemio in myeloma patients: release of m-l-sarcolysin in vivo and in vitro

Peptichemio (PTC) is a mixture of six synthetic oligopeptides, each of which contains the alkylating residue m-[di(2-chloroethyl)amino]-l-phenylalanine (l-mSL). The fate of PTC was investigated in eight patients with multiple myeloma after intravenous infusion of the drug. The quantitative analysis of the plasma samples was performed by liquid chromatography with fluorometric detection. l-mSL was rapidly released from the peptides and reached its maximal plasma concentration at the end of the infusion. Its median elimination half-life was 1.73 (range, 0.72-2.41) h. It was possible to follow the concentration of only one of the peptides, l-mSL-l-Arg(NO₂)-l-Nval·OEt, during and shortly after the infusion of PTC. The stability of l-mSL and the peptides was studied in buffer solution (pH 7.3), plasma, and blood. The stability of some of the peptides was drastically decreased in blood, the degradation half-lives being only about 1 min. We conclude that l-mSL plays an important role in the mechanism of action of PTC.