Effect of liver failure on the pharmacokinetics of cyclophosphamide

The pharmacokinetics of cyclophosphamide was investigated in 7 patients in severe liver failure. The pharmacokinetic data were compared with those derived from a matched control group of patients with normal liver function. The half-life (t1/2) of cyclophosphamide following intravenous administration in patients with liver failure was 12.5 +/- 1.0 h (m +/- SD), which was significantly longer than in the normal controls in whom it was 7.6 +/- 1.4 h (p less than 0.001). The mean total body clearance (Clt) was significantly smaller in liver failure at 44.8 + 8.61 X kg-1 than in the controls in whom it was 63.0 +/- 7.61 X kg-1 (p less than 0.01). It is concluded that severe liver disease has a significant effect on the disposition of cyclophosphamide, and that it could lead to accumulation of the drug in the body.