Rapid development of enhanced clearance after high-dose cyclophosphamide

M. J. Moore, R. W. Hardy, J. J. Thiessen, S. J. Soldin, C. Erlichman

Research output: Contribution to journalArticle

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Abstract

We have studied the disposition of cyclophosphamide, its major cytotoxic metabolite phosphoramide mustard, and the synthetic glucocorticoid dexamethasone in nine patients receiving high-dose cyclophosphamide daily for 2 days before bone marrow transplantation. The total body clearance of cyclophosphamide was observed to increase from 93 ± 27 ml/min on the first day to 178 ± 83 ml/min on the second day. This was associated with an increase in the clearance of dexamethasone from 369 ± 104 ml/min to 526 ± 123 ml/min. An increased rate of formation of phosphoramide mustard with higher peak concentrations was also seen. Simulation studies show that these changes are most likely the result of an increase in the hepatic metabolism of cyclophosphamide. These results show that high-dose cyclophosphamide causes an increase in its own clearance and that of dexamethasone through an apparent induction of hepatic-metabolizing enzymes detectable 24 hours after initial exposure to cyclophosphamide.

Original languageEnglish (US)
Pages (from-to)622-628
Number of pages7
JournalClinical Pharmacology and Therapeutics
Volume44
Issue number6
StatePublished - Dec 1988
Externally publishedYes

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Cyclophosphamide
Dexamethasone
Liver
Bone Marrow Transplantation
Glucocorticoids
Enzymes
phosphoramide mustard

ASJC Scopus subject areas

  • Pharmacology

Cite this

Moore, M. J., Hardy, R. W., Thiessen, J. J., Soldin, S. J., & Erlichman, C. (1988). Rapid development of enhanced clearance after high-dose cyclophosphamide. Clinical Pharmacology and Therapeutics, 44(6), 622-628.

Rapid development of enhanced clearance after high-dose cyclophosphamide. / Moore, M. J.; Hardy, R. W.; Thiessen, J. J.; Soldin, S. J.; Erlichman, C.

In: Clinical Pharmacology and Therapeutics, Vol. 44, No. 6, 12.1988, p. 622-628.

Research output: Contribution to journalArticle

Moore, MJ, Hardy, RW, Thiessen, JJ, Soldin, SJ & Erlichman, C 1988, 'Rapid development of enhanced clearance after high-dose cyclophosphamide', Clinical Pharmacology and Therapeutics, vol. 44, no. 6, pp. 622-628.
Moore MJ, Hardy RW, Thiessen JJ, Soldin SJ, Erlichman C. Rapid development of enhanced clearance after high-dose cyclophosphamide. Clinical Pharmacology and Therapeutics. 1988 Dec;44(6):622-628.
Moore, M. J. ; Hardy, R. W. ; Thiessen, J. J. ; Soldin, S. J. ; Erlichman, C. / Rapid development of enhanced clearance after high-dose cyclophosphamide. In: Clinical Pharmacology and Therapeutics. 1988 ; Vol. 44, No. 6. pp. 622-628.
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