Renal function in the elimination of oral melphalan in patients with multiple myeloma

Pharmacokinetic studies in 11 patients with multiple myeloma were undertaken on the first and last days of one course of chemotherapy. The drug was administered PO in single doses of 6-14 mg daily. Melphalan concentrations were determined by high-performance liquid chromatography. The interpatient variability of pharmacokinetic parameters noted by other authors was observed. Regression analysis showed a significant positive correlation between the elimination rate constant for melphalan and renal function (P = 0.003). The form of the line which describes the overall elimination rate constant for melphalan is given by the equation: Kel = 5.67 X 10(-3) + [4.90 X 10(-5) X GFR]. There was also a significant negative correlation between renal function and the area under the plasma melphalan concentration/time curve (P = 0.006). In vitro stability studies of melphalan in plasma at 37 degrees C and pharmacokinetic data suggest that hydrolysis and renal clearance are the major mechanisms of melphalan elimination. This work shows quantitatively the relationship between renal function and drug elimination and how the data may be used in predicting melphalan half-life from creatinine clearance.