TY - JOUR T1 - Urinary Excretion of Cyclophosphamide in Humans, Determined by Phosphorus-31 Nuclear Magnetic Resonance Spectroscopy JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 418 LP - 428 VL - 26 IS - 5 AU - Claire Joqueviel AU - Robert Martino AU - Veronique Gilard AU - Myriam Malet-Martino AU - Pierre Canal AU - Ulf Niemeyer Y1 - 1998/05/01 UR - http://dmd.aspetjournals.org/content/26/5/418.abstract N2 - Phosphorus-31 NMR spectroscopy was used to analyze urine samples from patients treated with cyclophosphamide (CP) on 2 consecutive days. CP and all of its known phosphorylated metabolites except the tautomeric pair 4-hydroxycyclophosphamide/aldophosphamide,i.e. carboxycyclophosphamide (CXCP), dechloroethylcyclophosphamide (DCCP), alcophosphamide, ketophosphamide, and phosphoramide mustard (PM), were determined. Several other signals corresponding to unknown CP-related compounds were observed. Seven of them were identified; all were hydrolysis products of CP or its metabolites (one from CP, two from CXCP, three from DCCP, and one from PM). Twenty-four-hour urinary excretion of unmetabolized CP was not significantly different on the first (17% of the daily administered dose) and second (16%) days of treatment. The amounts of phosphorylated metabolites excreted in 24-hr urine samples were much higher after the second CP dose (37%) than after the first (20%), suggesting autoinduction of CP metabolism. CXCP and its two degradation products (accounting for 7–10% of CXCP) were by far the major metabolites (11.5 and 23% after the first and second doses, respectively). DCCP plus its degradation products and alcophosphamide each represented 2–3% on the first day of treatment and 5% on the second day of treatment. Levels of PM and its degradation products were extremely low (0.3 and 0.6% after the first and second CP doses, respectively), as were those of ketophosphamide (0.4 and 0.6% on the first and second days of treatment, respectively). We noted only modest interpatient variation in excreted levels of CP and all of its metabolites. The American Society for Pharmacology and Experimental Therapeutics ER -