TY - JOUR
T1 - Blood levels and alkylating metabolites of cyclophosphamide in the mouse after Iv or oral administration
AU - Struck, R. F.
AU - Alberts, D. S.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1984
Y1 - 1984
N2 - Blood levels of cyclophosphamide (CPA) and its alkylating metabolites in mice were determined after iv or oral administration of a 200-mg/kg dose of radiolabeled CPA. Individual metabolites (4-hydroxy-CPA, 4-keto-CPA, alcophosphamide, dechloroethyl-CPA, carboxyphosphamide, and phosphoramide mustard) were isolated from blood by solvent extraction and by thin-layer chromatography. Area-under-the-blood-decay-curve (AUC) values were determined for CPA and its alkylating metabolites to provide a basis for comparison of systemic exposure by iv or oral treatment. The total AUC values for alkylating metabolites of CPA was observed to be greater after iv administration, and AUC values for each of the individual metabolites were greater after iv treatment, except for the minor metabolite alcophosphamide. The methods in this study have been applied to one patient to data and will be used in future studies with other patients to determine relative AUC values for the oncolytic CPA metabolites 4-hydroxy-CPA and phosphoramide mustard.
AB - Blood levels of cyclophosphamide (CPA) and its alkylating metabolites in mice were determined after iv or oral administration of a 200-mg/kg dose of radiolabeled CPA. Individual metabolites (4-hydroxy-CPA, 4-keto-CPA, alcophosphamide, dechloroethyl-CPA, carboxyphosphamide, and phosphoramide mustard) were isolated from blood by solvent extraction and by thin-layer chromatography. Area-under-the-blood-decay-curve (AUC) values were determined for CPA and its alkylating metabolites to provide a basis for comparison of systemic exposure by iv or oral treatment. The total AUC values for alkylating metabolites of CPA was observed to be greater after iv administration, and AUC values for each of the individual metabolites were greater after iv treatment, except for the minor metabolite alcophosphamide. The methods in this study have been applied to one patient to data and will be used in future studies with other patients to determine relative AUC values for the oncolytic CPA metabolites 4-hydroxy-CPA and phosphoramide mustard.
UR - http://www.scopus.com/inward/record.url?scp=0021282243&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021282243&partnerID=8YFLogxK
M3 - Article
C2 - 6722832
AN - SCOPUS:0021282243
VL - 68
SP - 765
EP - 770
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 5
ER -