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Clinical pharmacology profile of vorinostat, a histone deacetylase inhibitor

Marian Iwamoto1, Evan J Friedman, Punam Sandhu

  • 1Department of Project Leadership and Management, Merck Sharp & Dohme Corp. a Subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. marian.iwamoto@merck.com

Cancer Chemotherapy and Pharmacology
|July 4, 2013
PubMed
Abstract

Insights

Vorinostat, a histone deacetylase inhibitor, shows favorable pharmacokinetics and a low potential for drug interactions, supporting its use in advanced cutaneous T cell lymphoma (CTCL) and other cancers.

Area of Science:

  • Pharmacology
  • Oncology
  • Drug Metabolism

Background:

  • Vorinostat is a histone deacetylase inhibitor with demonstrated preclinical and clinical activity in various cancers.
  • It is currently approved for advanced cutaneous T cell lymphoma (CTCL).
  • Ongoing research explores its use in other solid tumors and hematological malignancies, as monotherapy or in combination.

Purpose of the Study:

  • To review the pharmacokinetic properties of vorinostat.
  • To summarize clinical pharmacology data, including dose proportionality and food effects.
  • To assess potential drug interactions and pharmacokinetic variability in special populations.

Main Methods:

  • Review of monotherapy pharmacokinetic data from multiple studies.
  • Literature review of published Phase I and II combination therapy pharmacokinetic data.
  • Analysis of pharmacokinetic data in special populations.

Main Results:

  • Vorinostat exhibits a favorable clinical pharmacology profile with dose-proportional pharmacokinetics and a modest food effect.
  • No significant pharmacokinetic differences were observed in special populations, including those with hepatic dysfunction.
  • Combination therapy data suggest a low propensity for drug interactions with vorinostat.

Conclusions:

  • Vorinostat's favorable pharmacokinetic and drug interaction profile facilitates its administration for advanced CTCL.
  • These properties are beneficial for its continued evaluation in other oncologic indications.
  • Further rigorous pharmacokinetic studies, including clinical drug interaction assessments, are warranted.

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