These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Pharmacokinetics of cyclophosphamide and its metabolites in bone marrow transplantation patients.
    Author: Ren S, Kalhorn TF, McDonald GB, Anasetti C, Appelbaum FR, Slattery JT.
    Journal: Clin Pharmacol Ther; 1998 Sep; 64(3):289-301. PubMed ID: 9757153.
    Abstract:
    OBJECTIVES: To characterize the pharmacokinetics of cyclophosphamide and 5 of its metabolites in bone marrow transplant patients and to identify the mechanism of the increase in 4-hydroxycyclophosphamide area under the plasma concentration-time curve (AUC) from day 1 to day 2 of cyclophosphamide administration. METHODS: Cyclophosphamide was administered by intravenous infusion (60 mg/kg over 1 hour, once a day) for 2 consecutive days to 18 patients. Cyclophosphamide and 4-hydroxycyclophosphamide concentration time data on day 1 and day 2 were fitted to a model to estimate 4-hydroxycyclophosphamide formation (CLf) and elimination (CLm) clearances. Erythrocyte aldehyde dehydrogenase-1 activity was measured ex vivo just before the first cyclophosphamide infusion was started (0 hours) and 24 hours after the second cyclophosphamide infusion (48 hours). RESULTS: From day 1 to day 2, the AUC of cyclophosphamide, deschloroethyl cyclophosphamide and phosphoramide mustard decreased 24.8%, 51%, and 29.4% (P < .02), the AUC of 4-hydroxycyclophosphamide and carboxyethylphosphoramide mustard increased 54.7% and 25% (P < .01), whereas the AUC of phosphoramide mustard was not significantly changed (P > .3). The CLf of 4-hydroxycyclophosphamide increased 60% (P < .001), its CLm decreased 27.7% (P < .001), and the fraction of cyclophosphamide dose converted to 4-hydroxycyclophosphamide increased 16% (P < .001) from day 1 to day 2. The activity of patient erythrocyte aldehyde dehydrogenase-1 decreased 23.3% (P < .02) from 0 hours to 48 hours. CONCLUSIONS: The AUC of 4-hydroxycyclophosphamide increased from day 1 to day 2 as a result of increased formation and decreased elimination clearances of 4-hydroxycyclophosphamide. Aldehyde dehydrogenase-1 activity appears to decline as a consequence of cyclophosphamide administration.
    [Abstract] [Full Text] [Related] [New Search]