Determination of the acute oral toxicity of theophylline in conscious dogs

I. J. MUNSIFF, B. C. MCKIERNAN, C. A. NEFF‐DAVIS, G. D. KORITZ

Research output: Contribution to journalArticlepeer-review

Abstract

Munsiff, I.J., McKiernan, B.C., Neff‐Davis, C.A. & Koritz, CD. Determination of the acute oral toxicity of theophylline in conscious dogs. J. vet. Pharmacol. Therap. 11, 381–389. The purpose of this study was to define the minimum toxic concentrations and clinical signs of theophylline toxicity in healthy, conscious dogs. Five dogs were dosed orally in a five‐way crossover design with sustained release theophylline (Theo‐Dur® tablets, Key Pharmaceuticals) at 0, 20, 40, 80, and 160 mg/kg. They were observed for a 9‐h period for clinical signs of toxicity which had been previously determined in a pilot study. These signs included sinus tachycardia and central nervous stimulation (manifested as restlessness, excitement, or vomition). The Physiotel® radiotransmitter telemetry system was used for the acquisition of the heart rate and ECG. Blood samples were obtained every hour for theophylline determination by high pressure liquid chromatography. The results showed that toxicity occurs at higher theophylline plasma concentrations in the dog (37–60 m̈g/ml) as compared to man (> 20 m̈g/ml) when dosed orally. Since current dosage regimens in dogs are designed to maintain trough‐peak theophylline plasma concentrations between 10 and 20 m̈g/ml, the results indicate that the upper limit of this range appears to be safe in the dog.

Original languageEnglish (US)
Pages (from-to)381-389
Number of pages9
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume11
Issue number4
DOIs
StatePublished - Dec 1988

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

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