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Belfayol-Pisanté, L. et al.

Belfayol-Pisanté, Guillevin, Tod, Fauvelle,

Pharmacokinetics of cyclophosphamide (CP) and 4-OH-CP/aldophosphamide in systemic vasculitis.

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.[1]

References

Pharmacokinetics of cyclophosphamide (CP) and 4-OH-CP/aldophosphamide in systemic vasculitis. Belfayol-Pisanté, L., Guillevin, L., Tod, M., Fauvelle, F. Fundamental & clinical pharmacology. (2000) [Pubmed]

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