Semi‐Mechanism‐Based Population Pharmacokinetic Modeling of the Hedgehog Pathway Inhibitor Vismodegib
نویسندگان
چکیده
منابع مشابه
Pharmacokinetic dose-scheduling study of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with locally advanced or metastatic solid tumors.
PURPOSE This study was designed to evaluate whether less frequent dosing [three times per week (TIW) or once weekly (QW)] of 150 mg vismodegib following a loading dose [150 mg once daily (QD) for 11 days] would result in similar safety, tolerability, and steady-state levels of total and unbound vismodegib as continuous QD dosing. EXPERIMENTAL DESIGN Sixty-seven patients with advanced solid tu...
متن کاملPharmacokinetic-pharmacodynamic analysis of vismodegib in preclinical models of mutational and ligand-dependent Hedgehog pathway activation.
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© 2014 Harborside Press® Skin cancer is the most common cancer type in the United States, affecting more than 3 million people nationally (Cirrone & Harris, 2012). Basal cell carcinoma (BCC) and squamous cell carcinoma are the two main types of nonmelanoma skin cancer, while the more serious form, melanoma, is in its own category. An estimated 80% of nonmelanoma skin cancers are BCCs (Sekulic e...
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Purpose: Vismodegib (GDC-0449) is a potent and selective inhibitor of the Hedgehog (Hh) pathway that shows antitumor activity in preclinical models driven bymutational or ligand-dependent activation of the Hh pathway.We wished to characterize the pharmacokinetic–pharmacodynamic (PK/PD) relationship of vismodegib in both model systems to guide optimal dose and schedule for vismodegib in the clin...
متن کاملCancer Therapy: Clinical Pharmacokinetic Dose-Scheduling Study of Hedgehog Pathway Inhibitor Vismodegib (GDC-0449) in Patients with Locally Advanced or Metastatic Solid Tumors
Purpose: This study was designed to evaluate whether less frequent dosing [three times per week (TIW) or once weekly (QW)] of 150 mg vismodegib following a loading dose [150 mg once daily (QD) for 11 days] would result in similar safety, tolerability, and steady-state levels of total and unbound vismodegib as continuous QD dosing. Experimental Design: Sixty-seven patients with advanced solid tu...
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ژورنال
عنوان ژورنال: CPT: Pharmacometrics & Systems Pharmacology
سال: 2015
ISSN: 2163-8306,2163-8306
DOI: 10.1002/psp4.12039