Abstract
Cyclophosphamide pharmacokinetics were investigated following administration to patients with systemic necrotizing angiitis. Ten patients (eight women and two men) received cyclophosphamide as a 1-h-rate-constant intravenous infusion at doses ranging from 600 to 1200 mg. All patients received concomitant oral prednisone (1 mg/kg/d). Blood samples were collected at the end of drug infusion and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h later. Serum cyclophosphamide concentrations were assayed by high pressure liquid chromatography. The peak serum cyclophosphamide levels ranged from 15.7 to 29.4 mg/L. The mean cyclophosphamide elimination half-life was 6.2 +/- 1.3 h (mean +/- SD). The mean apparent volume of distribution and mean total plasma clearance were, respectively, 0.75 +/- 0.22 L/kg (mean +/- SD) and 83 +/- 22 mL/min (mean +/- SD). These results obtained in systemic vasculitic diseases were consistent with those observed in other studies with cancer patients receiving comparable doses of cyclophosphamide.
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