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Cyclophosphamide was given as IV doses of 50 mg/kg/day on each of four successive days as treatment for ovarian and lung cancer. Blood samples were taken at regular intervals and analysed for cyclophosphamide by gas liquid chromatography. The plasma half-lives (t 1/2) and volumes of distribution (V D) were calculated for each of the treatment days; t 1/2 was found to decrease with subsequent doses whereas V D was not significantly changed.

Following simultaneous i.v. administration of a mixture of [4-14C]cyclophosphamide (14C-CP) and [side-chain 3H]CP to rats, a metabolite containing predominantly 3H radioactivity was excreted in the urine. The 3H-labelled urinary metabolite was identified as 2-chloroacetaldehyde. Chloro[3H]acetaldehyde accounted for approx. 3.8% of urinary 3H radioactivity. The importance of chloroacetaldehyde as a toxic metabolite of CP is discussed, particularly in relation to haemorrhagic bladder disease.

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