Progressive Trial on Clinical Services in a Hospital(V). Pharmacokinetics of Cyclophosphamide in Plasma and Cerebrospinal Fluid during Mobilization of Blood Stem Cells by High Dose Chemotherapy.

Abstract

We performed a clinical pharmacy based service on the therapeutic drug monitoring (TDM) of cyclophosphamide (CP) during high dose CP chemotherapy in order to mobilize the peripheral blood stem cell in a 42-year-old man with glioblastoma. The patient was infused with 2000 mg CP for 3.75 hours. Samples of blood and of cerebrospinal fluid (CSF) were obtained. Both the CP and active metabolite of CP, nor-mustard (NM), concentrations were measured by the colorimetric assay method used 4-(p-Nitrobenzyl) pyridine (NBP) and the phamacokinetic parameters of CP and NM in plasma and CSF were estimated used a compartment model. The plasma concentration of CP peaked at the end of infusion, and there after decreased in a bi-exponential decay manner. The CSF concentration of CP peaked at the end of infusion, and then decreased in a mono-exponential decay manner. The plasma concentration of NM peaked 2 hours after drug administration and then gradually decreased. NM was not detectable in CSF. The area under the concentration-time curve (AUC) for the CSF of CP comprised only about 16.7% of that found in plasma. Those results suggested that the cytotoxicity of CP and NM in CSF was low because of the permeability of CP and NM into CSF was low.