Plasma Melphalan and Prednisolone Concentrations During Oral Therapy for Multiple Myeloma

Nine patients with myeloma were studied over 13 oral administrations of 10 mg melphalan and 5-10 mg prednisolone. Plasma melphalan concentrations were estimated by high-pressure liquid chromatography, prednisolone concentrations by quantitative thin-layer chromatography. The mean plasma half-life of unchanged melphalan was 0.9 +/- 0.5 (SD) h. The 'lag-time' before melphalan was detected in the plasma varied from 1 to 4 h, the mean peak concentration was 96 +/- 21 ng/ml, and the mean area under the plasma concentration by time curve was 160 +/- 78 ng h/ml. This variability was consistent with observations made elsewhere following much higher oral doses of melphalan and illustrates the relatively wide interindividual variability of absorption. Observations made in the same subjects on two separate occasions showed lower variability. The melphalan elimination rate was not significantly affected by moderate impairment of creatinine clearance (to 31 ml/min). Absorption of prednisolone in five of these patients was apparently normal and unaffected by concurrent administration of melphalan.