• Lauriane Goldwirt, Kevin Beccaria, Alexandre Carpentier, Robert Farinotti, and Christine Fernandez.
• Clinical Pharmacy Department - EA 4123, College of Pharmacy, Paris-Sud University, 5 rue Jean Baptiste Clement, 92296, Chatenay Malabry, France, lauriane.goldwirt@u-psud.fr.
• Cancer Chemother. Pharmacol. 2014 Jul 1; 74 (1): 185-93.

AbstractGlioblastoma (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.

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