Pharmacokinetics and pharmacodynamics of suberoylanilide hydroxamic acid in cats

S. J. Mcdonnel, Lisa A Tell, Brian G Murphy

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Suberoylanilide hydroxamic acid (SAHA), or vorinostat, is a histone deacetylase inhibitor approved for use as chemotherapy for lymphoma in humans. The goal of this study was to establish pharmacological parameters of SAHA in cats. Our interest in treating cats with SAHA is twofold: as an anticancer chemotherapeutic and as antilatency therapy for feline retroviral infections. Relying solely on data from studies in other animals would be inappropriate as SAHA is partially metabolized by glucuronidation, which is absent in feline metabolism. SAHA was administered to cats intravenously (2 mg/kg) or orally (250 mg/m2, ~17 mg/kg) in a cross-over study design. Clinically, SAHA was well tolerated at these dosages as no abnormalities were noted following administration. The pharmacokinetics of SAHA in cats was found to be similar to that of dogs, but the overall serum drug exposure was much less than that of humans at an equivalent dose. The pharmacodynamic effect of an increase in acetylated histone proteins in blood was detected after both routes of administration. An increased oral dose of 60 mg SAHA/kg administered to one animal resulted in a surprisingly modest increase in peak drug concentration, suggesting possible saturation of absorption kinetics. This study provides a foundation for future studies of the clinical efficacy of SAHA in treating feline disease.

Original languageEnglish (US)
Pages (from-to)196-200
Number of pages5
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume37
Issue number2
DOIs
StatePublished - 2014

Fingerprint

hydroxamic acids
pharmacology
pharmacokinetics
Cats
Pharmacokinetics
cats
Felidae
Cross-Over Studies
dosage
Cat Diseases
drugs
histone deacetylase
cat diseases
vorinostat
Histone Deacetylase Inhibitors
lymphoma
histones
drug therapy
blood proteins
clinical trials

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

Cite this

Pharmacokinetics and pharmacodynamics of suberoylanilide hydroxamic acid in cats. / Mcdonnel, S. J.; Tell, Lisa A; Murphy, Brian G.

In: Journal of Veterinary Pharmacology and Therapeutics, Vol. 37, No. 2, 2014, p. 196-200.

Research output: Contribution to journalArticle

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