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Merck

Irinotecan and temozolomide brain distribution: a focus on ABCB1.

Cancer chemotherapy and pharmacology (2014-05-29)
Lauriane Goldwirt, Kevin Beccaria, Alexandre Carpentier, Robert Farinotti, Christine Fernandez
要旨

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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製品内容

Sigma-Aldrich
テモゾロミド, ≥98% (HPLC)
Sigma-Aldrich
テオフィリン, anhydrous, ≥99%, powder
Sigma-Aldrich
(S)-(+)-カンプトテシン, ≥90% (HPLC), powder
Sigma-Aldrich
イリノテカン 塩酸塩, topoisomerase inhibitor
Sigma-Aldrich
7-エチル-10-ヒドロキシカンプトテシン, ≥98% (HPLC), powder
USP
テオフィリン, United States Pharmacopeia (USP) Reference Standard
Supelco
テオフィリン, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
テモゾロミド, Pharmaceutical Secondary Standard; Certified Reference Material
テオフィリン, European Pharmacopoeia (EP) Reference Standard
Supelco
テモゾロミド, VETRANAL®, analytical standard