Published in:
01-01-2011 | Original Article
Penetration of ifosfamide and its active metabolite 4-OH-ifosfamide into cerebrospinal fluid of patients with CNS malignancies
Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2011
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Purpose
The aim of this study was to examine the penetration of ifosfamide (IFO) and 4-hydroxy-ifosfamide (4-OH-IFO) into the CSF of human adults and to evaluate the influence of blood–CSF barrier (BCB) function.
Methods
In 12 adult patients with a malignant CNS disease treated with IFO 1,300–2,000 mg/m2/d as a 3-hour intravenous infusion, 17 CSF samples were collected within 10 min after the end of IFO infusion. In 8 of these patients, the CSF was obtained in up to 5 sequential 2-ml portions to detect a potential caudocranial concentration gradient. Additionally, blood was collected before treatment and immediately following IFO infusion.
Results
IFO was detected in all 17 CSF samples at a median concentration of 79.24 μmol/l (39.27–176.73) and a median CSF/plasma ratio of 0.38 (0.18–0.72). 4-OH-IFO was detected in 11 CSF samples from 7 patients at a median concentration of 4.1 μmol/l (2.44–36.03) and a median CSF/plasma ratio of 3.07 (0.62–29.12). 4-OH-IFO was undetectable in 6 CSF samples from 5 patients and in one plasma sample. Both CSF drug concentrations and their CSF/plasma quotients neither correlated with steroid comedication nor with albumin quotients (QAlb).
Conclusions
Both IFO and 4-OH-IFO can penetrate into the CSF of human adults without a correlation to CSF turnover. In contrast to IFO, 4-OH-IFO CSF penetration is not reliable with levels ranging between undetectable and exceeding those in the corresponding plasma.