Pharmacokinetics of oral and intravenous melphalan during routine treatment of multiple myeloma

Abstract

Plasma melphalan levels have been measured in nine (mostly stage IIIA) multiple myeloma patients after therapeutic doses of drug had been given p.o. and i.v. A new isocratic high-pressure liquid chromatographic (HPLC) method with a sensitivity limit o 5 ng/ml was used to quantify the melphalan. Patients receiving 8-28.5 mg melphalan i.v. showed alpha and beta plasma decays with half-lives of 7.7 +/- 3.3 (mean +/- S.D.) and 83 +/- 14 min respectively. The apparent volume of the central compartment was 12.8 +/- 4.3 1, and the total volume of distribution was 0.62 +/- 0.21 l/kg. Very variable absorption was seen in the same patients after receiving 5-12 mg melphalan p.o. The half-life of the absorption phase varied from 2.1 to 62.1 min (22.8 +/- 18.1 min) with delays (before absorption started) of 0-113 min. The fraction of dose absorbed varied from 0.32 to 1.03 (0.72 +/- 0.23), and the half-life of the beta phase was 92 +/- 27 min. The type of breakfast eaten before p.o. melphalan was found to correlate with the fraction of drug absorbed.