Drug-drug interaction pharmacokinetic study with the Raf kinase inhibitor (RKI) BAY 43-9006 administered in combination with irinotecan (CPT-11) in patients with solid tumors

Mross, K.; Steinbild, Simone; Baas, F.; Reil, M; Buss, Peter; Mersmann, S.; Voliotis, D.; Schwartz, Brian; Brendel, E.

doi:10.5414/cpp41618

Cited by 23 publications

(14 citation statements)

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“…The AUC last was 3250 ng h/mL. Overall, the pharmacokinetic profile is consistent with previous reports with the exception of a prominent secondary peak due to enterohepatic recirculation [13,17,19].…”

Section: Plasma Concentration-time Profilesupporting

confidence: 90%

“…Here, we describe a rapid, sensitive analytical method for the determination of sorafenib concentrations in human plasma based on LC/MS/MS with electrospray positive ionization after a single protein precipitation with acetonitrile. Based on previous published pharmacokinetic data, the assay range of 7.3-7260 ng/mL should be sufficient to characterize the clinical pharmacology of sorafenib in clinical trials being conducted at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins [13,17,19]. …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A rapid and sensitive method for determination of sorafenib in human plasma using a liquid chromatography/tandem mass spectrometry assay

Zhao

Rudek

et al. 2007

Journal of Chromatography B

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Section: Plasma Concentration-time Profilesupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

A rapid and sensitive method for determination of sorafenib in human plasma using a liquid chromatography/tandem mass spectrometry assay

Zhao

Rudek

et al. 2007

Journal of Chromatography B

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“…In contrast, clinical studies conducted by Bayer and Onyx Pharmaceuticals, Inc. with the RAF kinase inhibitor sorafenib (tosylate salt of BAY 43-9006 (1)) have been promising [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53]. Sorafenib is a multi-kinase inhibitor from the diaryl urea family.…”

Section: The Erk Pathway As a Target For Cancer Drug Discoverymentioning

confidence: 96%

“…• antisense inhibitors of RAF expression (ISIS-5132) [33][34][35][36]. • small molecule inhibitors of RAF (BAY 43-9006 (1)) [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53]. • small molecule inhibitors of MEK (PD-0325901 (5) and ARRY-142886 (6)) [54][55][56][57][58].…”

Section: The Erk Pathway As a Target For Cancer Drug Discoverymentioning

confidence: 99%

Recent Advances in the Research and Development of RAF Kinase Inhibitors

Smith¹,

Dumas²,

Adnane³

et al. 2006

CTMC

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The RAS-RAF-MEK-ERK signaling pathway (ERK pathway) plays a key role in tumorigenesis and cancer progression. Mutations of RAS or B-RAF lead to a constitutive activation of the ERK pathway, which ultimately results in increased cell division, and cell survival. This review article focuses on the recent literature related to ERK pathway inhibitors, with a particular emphasis on RAF kinase inhibitors. Preclinical and clinical data for the RAF kinase inhibitor sorafenib (BAY 43-9006 tosylate), that was recently approved in the US for the treatment of advanced renal cell carcinoma, are also outlined.

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“…For example, preliminary results from phase I/II trials combining BAY 43-9006 with doxorubicin [53], oxaliplatin [54], irinotecan [55], gemcitabine [56], carboplatin, and paclitaxel [57] have been reported. In all of these trials, pharmacokinetic data did not show any significant interaction between BAY 43-9006 and the cytotoxic compound nor did clinical data suggest enhanced toxicity by addition of BAY 43-9006.…”

Section: Combination Studiesmentioning

confidence: 99%

Raf Kinase Inhibitors in Oncology

Strumberg¹,

Seeber²

2005

Oncol Res Treat

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The importance of the MAP kinase pathway, which includes the kinases Raf, MEK1/2, and ERK1/2, for the proliferation and survival of tumor cells recently increased with the discovery of activating BRAF mutations in human tumors. Therefore, in addition to a role in controlling tumors with Ras mutations and activated growth factor receptors, inhibitors of Raf kinase may harbor therapeutic potential in tumors carrying a BRAF oncogene. A variety of agents have been discovered to interfere with Raf kinase, including antisense oligonucleotides and small molecules. These inhibitors prevent the expression of Raf protein, block Ras/Raf interaction, or obstruct its kinase activity. Raf inhibitors that are currently undergoing clinical evaluation show promising signs of anti-cancer efficacy with a very tolerable safety profile. Clinically most advanced is the Raf inhibitor BAY 43-9006, which recently entered phase III clinical testing. This review addresses the rationale for targeting Raf kinase and the current status of various pharmacological approaches.

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Drug-drug interaction pharmacokinetic study with the Raf kinase inhibitor (RKI) BAY 43-9006 administered in combination with irinotecan (CPT-11) in patients with solid tumors

Cited by 23 publications

References 0 publications

A rapid and sensitive method for determination of sorafenib in human plasma using a liquid chromatography/tandem mass spectrometry assay

A rapid and sensitive method for determination of sorafenib in human plasma using a liquid chromatography/tandem mass spectrometry assay

Recent Advances in the Research and Development of RAF Kinase Inhibitors

Raf Kinase Inhibitors in Oncology

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