AI Article Synopsis
- The study investigates how well ifosfamide (IFO) and its metabolite, 4-hydroxy-ifosfamide (4-OH-IFO), penetrate into the cerebrospinal fluid (CSF) of adults with cancer.
- It involved 12 patients receiving IFO, with CSF samples collected shortly after treatment to measure drug concentrations and assess any concentration gradients.
- Results showed IFO consistently penetrated the CSF, while 4-OH-IFO levels varied significantly and did not reliably correlate with other factors, suggesting variable effectiveness in reaching the CSF.
Article Abstract
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/m(2)/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.
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| http://dx.doi.org/10.1007/s00280-010-1274-4 | DOI Listing |
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