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Irinotecan and temozolomide brain distribution: a focus on ABCB1

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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.

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Abbreviations

CPT-11:

Irinotecan

SN-38:

7-Ethyl-10-hydroxycamptothecin

TMZ:

Temozolomide

AUC:

Area under the curve

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Acknowledgments

The authors thank Stella Ghouti for grammatical English corrections.

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Authors and Affiliations

  1. Clinical Pharmacy Department - EA 4123, College of Pharmacy, Paris-Sud University, 5 rue Jean Baptiste Clement, 92296, Chatenay Malabry, France

    Lauriane Goldwirt, Robert Farinotti & Christine Fernandez

  2. Department of Neurosurgery, Pitie-Salpetriere Hospital, AP-HP, 75013, Paris, France

    Kevin Beccaria & Alexandre Carpentier

  3. Pharmacy Department, Saint Antoine Hospital, AP-HP, 75012, Paris, France

    Christine Fernandez

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  1. Lauriane Goldwirt
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  2. Kevin Beccaria
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Correspondence to Lauriane Goldwirt.

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Goldwirt, L., Beccaria, K., Carpentier, A. et al. Irinotecan and temozolomide brain distribution: a focus on ABCB1. Cancer Chemother Pharmacol 74, 185–193 (2014). https://doi.org/10.1007/s00280-014-2490-0

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