Biliary elimination of cyclophosphamide in man

A 72-year-old male with a lymphoma and obstructive jaundice received 900 mg cyclophosphamide IV as a part of a chemotherapeutic regimen whilst external biliary drainage was in progress. Plasma, urinary, and biliary pharmacokinetics of cyclophosphamide and nitrobenzylpyridine (NBP)-alkylating metabolites were studied. In 32 h 891 ml bile was collected, and this contained unchanged cyclophosphamide and NBP-alkylating material. Despite fluctuations in biliary flow, estimates of the half-life of cyclophosphamide from plasma, urine, and bile were similar. Good correlation existed between plasma and biliary cyclophosphamide concentrations after the initial plasma had been completed. The ratio of bile to plasma concentrations was 0.7 and showed no time dependence, as evidenced by a lack of hysteresis in the correlation curve. Of the administered dose, 3.5% was excreted as unchanged cyclophosphamide in the bile over 32 h. NBP-alkylating activity was found in bile up to 25 h but not after this time, despite the presence of unchanged cyclophosphamide in plasma. NBP-alkylating material was not found in the bile when it could not be detected in plasma, and vice versa.