The objective of this research application is to determine the pharmacokinetic parameter AUC (area-under-the plasma decay curve) for cyclophosphamide and its oncolytically efficacious metabolites, 4-hydroxycyclophosphamide and phosphoramide mustard, in blood plasma of cancer patients treated intravenously with cyclophosphamide with or without prior oral treatment for two weeks with the antiulcer drug ranitidine. The goal is to determine the effect of ranitidine (1) on plasma availability of the two oncolytic metabolites of CPA and consequent, relative oncolytic potential and (2) hematologic toxicity. Methodology will consist of blood collection, plasma separation and extraction, thin-layer chromatography of extracts, and radioassay.
| Alberts, D S; Mason-Liddil, N; Plezia, P M et al. (1991) Lack of ranitidine effects on cyclophosphamide bone marrow toxicity or metabolism: a placebo-controlled clinical trial. J Natl Cancer Inst 83:1739-42 |
