title: Pharmacokinetics of cyclophosphamide (CP) and 4-OH-CP/aldophosphamide in systemic vasculitis.
abstract: Cyclophosphamide given in association with corticosteroids has markedly improved the prognosis of systemic vasculitis. Little information has been reported on cyclophosphamide pharmacokinetics in these diseases and data evaluating its metabolite, 4-hydroxycyclophosphamide/aldophosphamide, pharmacokinetics and concentrations are lacking. Cyclophosphamide was administered as a 1-h intravenous infusion every 3 weeks for six cycles to ten vasculitis patients. Serum cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide concentrations were assayed on the first cycle of the treatment by reversed-phase high-pressure liquid chromatography with ultraviolet detection. The mean (+/- SD) 4-hydroxycyclophosphamide/aldophosphamide and cyclophosphamide areas under the serum concentration-time curves were, respectively, 1.86 +/- 1.12 and 154.1 +/- 62.7 mg/L x h with a ratio of 1.30 +/- 0.76%. The mean maximum serum 4-hydroxycyclophosphamide/aldophosphamide was reached 2.3 h after cyclophosphamide administration. The mean (+/- SD) cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide half-lives were, respectively, 5.5 +/- 3.1 and 7.6 +/- 2.3 h. The results are consistent with those obtained for cancer patients, in spite of a wide interpatient variability of concentrations and pharmacokinetic parameters.
authors.affiliation: Laboratory of Pharmacokinetics and Clinical Pharmacy, Hôpital de Montfermeil, France. lpisante@ch-montfermeil.fr
authors.forename: L
authors.initials: L
authors.lastname: Belfayol-Pisanté
authors.forename: L
authors.initials: L
authors.lastname: Guillevin
authors.forename: M
authors.initials: M
authors.lastname: Tod
authors.forename: F
authors.initials: F
authors.lastname: Fauvelle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010752:Phosphoramide Mustards / Q000378:metabolism*; D014657:Vasculitis / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D010752:Phosphoramide Mustards; C012358:4-hydroxycyclophosphamide; C006446:aldophosphamide; D003520:Cyclophosphamide