1. Irinotecan and temozolomide brain distribution: a focus on ABCB1.
- Author
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Goldwirt, Lauriane, Beccaria, Kevin, Carpentier, Alexandre, Farinotti, Robert, and Fernandez, Christine
- Subjects
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BRAIN tumor treatment , *IRINOTECAN , *TEMOZOLOMIDE , *CANCER radiotherapy , *TUMORS in adolescence , *PHARMACOKINETICS - Abstract
Glioblastoma (GBM), the most common primary brain tumor in adults, is usually rapidly fatal with median survival duration of only 15 months and a 3-year survival rate of <7 %. Temozolomide (TMZ) is the only anticancer drug that has improved survival in GBM when administered with concomitant radiotherapy. Irinotecan (CPT-11) has also shown efficacy in recurrent gliomas monotherapy with moderate response. As the efficacy of GBM treatments relies on their brain distribution through the blood-brain barrier (BBB), the aim of the present work was to study, on an in vivo model, the brain distribution of TMZ, CPT-11 and its active metabolite, SN-38. We have focussed on the role of ABCB1, the main efflux transporter at the BBB level, through pharmacokinetics studies in CF1 mdr1a (+/+) and mdr1a (−/−) mice. Our results show that TMZ, CPT-11 and SN-38 are transported by ABCB1 at the BBB level with brain/plasma ratios of 1.1, 2.1 and 2.3, respectively. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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