P-glycoprotein, CYP3A, and plasma carboxylesterase determine brain and blood disposition of the mTOR Inhibitor everolimus (Afinitor) in mice.

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作者： Seng Chuan,Tang ^[1] ; Rolf W,Sparidans ^[1] ; Ka Lei,Cheung ^[1] ; Tatsuki,Fukami ^[1] ; Selvi,Durmus ^[1] ; Els,Wagenaar ^[1] ; Tsuyoshi,Yokoi ^[1] ; Bart J M,van Vlijmen ^[1] ; Jos H,Beijnen ^[2] ; Alfred H,Schinkel ^[3]

作者单位： Authors' Affiliations: Division of Molecular Oncology, the Netherlands Cancer Institute; Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam; Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht; Department of Thrombosis and Hemostasis, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands; and Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Japan. ^[1] Authors' Affiliations: Division of Molecular Oncology, the Netherlands Cancer Institute; Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam; Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht; Department of Thrombosis and Hemostasis, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands; and Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, JapanAuthors' Affiliations: Division of Molecular Oncology, the Netherlands Cancer Institute; Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam; Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht; Department of Thrombosis and Hemostasis, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands; and Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Japan. ^[2] Authors' Affiliations: Division of Molecular Oncology, the Netherlands Cancer Institute; Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam; Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht; Department of Thrombosis and Hemostasis, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands; and Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Japan a.schinkel@nki.nl. ^[3]