Pharmacokinetics of high-dose intravenous melphalan in children and adults with forced diuresis

Abstract

The pharmacokinetic parameters of the alkylating agent melphalan were determined in 15 children and 11 adults with advanced malignant solid tumors. High IV bolus doses of 140 mg/m² were given under standard hyperhydration conditions and followed by autologous bone marrow grafting. In all cases the time-concentration curves could be best fitted to a biexponential pattern. A high scattering of drug concentrations was observed in our patients, the disposition half-lives ranging in the whole group from 17.8 to 71.2 min. The areas under the curves also showed a wide variation, ranging from 175 to 682 mg l^-1 min^-1. In all patients, melphalan levels in plasma were unmeasurable at 8 h or earlier, indicating that bone marrow can be safely reinfused at that time. No difference was apparent between children and adults regarding the drug pharmacokinetics. In each of 11 cerebrospinal fluid samples drawn 45–150 min after melphalan administration, drug levels were unmeasurable.