Pharmacokinetics of cyclophosphamide and alkylating activity in man after intravenous and oral administration.

Abstract

1 Plasma cyclophosphamide levels were estimated by gas-chromatography in seven patients following intravenous and oral cyclophosphamide administration. Plasma alkylating activity was determined by the nitrobenzyl pyridine (NBP) reaction. 2 The plasma Ti after intravenous administration ranged from 5.97 to 12.37 h but after oral administration was shorter, 1.32-6.8 h. The mean total body clearance was 66.6 ml kg-' h-' after intravenous dosing and 93.1 ml kg-' h-' following oral dosing. Vd was 0.71 (0.10 s.d.) 1 kg-' suggesting that cyclophosphamide is distributed largely in body water. 3 The mean hepatic extraction ratio was 0.25, indicating a modest first pass metabolism. The metabolic clearance was 3.72 1 kg-' and the intrinsic hepatic clearance 5.17 1 kg-'. 4 The mean renal clearance was 4.8 ml kg-' h-' with 6.5% of the administered dose excreted unchanged in the urine suggesting tubular reabsorption of cyclophosphamide.