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Cancer Chemotherapy and Pharmacology

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01.09.2013 | Review Article

Clinical pharmacology profile of vorinostat, a histone deacetylase inhibitor

verfasst von: Marian Iwamoto, Evan J. Friedman, Punam Sandhu, Nancy G. B. Agrawal, Eric H. Rubin, John A. Wagner

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2013

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Abstract

Purpose

Vorinostat is a histone deacetylase inhibitor that has demonstrated preclinical activity in numerous cancer models. Clinical activity has been demonstrated in patients with a variety of malignancies. Vorinostat is presently indicated for the treatment of patients with advanced cutaneous T cell lymphoma (CTCL). Clinical investigation is ongoing for therapy of other solid tumors and hematological malignancies either as monotherapy or in combination with other chemotherapeutic agents. This review summarizes the pharmacokinetic properties of vorinostat.

Methods

Monotherapy pharmacokinetic data across a number of pharmacokinetic studies were reviewed, and data are presented. In addition, literature review was performed to obtain published Phase I and II pharmacokinetic combination therapy data to identify and characterize potential drug interactions with vorinostat. Pharmacokinetic data in special populations were also reviewed.

Results

The clinical pharmacology profile of vorinostat is favorable, exhibiting dose-proportional pharmacokinetics and modest food effect. There appear to be no major differences in the pharmacokinetics of vorinostat in special populations, including varying demographics and hepatic dysfunction. Combination therapy pharmacokinetic data indicate that vorinostat has a low propensity for drug interactions.

Conclusions

Vorinostat’s favorable clinical pharmacology and drug interaction profile aid in the ease of administration of vorinostat for the treatment of advanced CTCL and will be beneficial in continued assessment for other oncologic indications. Although a number of studies have been conducted to elucidate the detailed pharmacokinetic profile of vorinostat, more rigorous assessment of vorinostat pharmacokinetics, including clinical drug interaction studies, will be informative.

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Pharmacokinetic data units were converted from mM to µM; mM units were likely a typographical error in the Badros et al. manuscript.

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Titel: Clinical pharmacology profile of vorinostat, a histone deacetylase inhibitor
verfasst von: Marian Iwamoto
Evan J. Friedman
Punam Sandhu
Nancy G. B. Agrawal
Eric H. Rubin
John A. Wagner
Publikationsdatum: 01.09.2013
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 3/2013
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-013-2220-z

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Springer Medizin

Clinical pharmacology profile of vorinostat, a histone deacetylase inhibitor

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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