Evaluation of the bioavailability and pharmacokinetics of two extended-release theophylline formulations in dogs

Jonathan F. Bach, Butch Kukanich, Mark G. Papich, Brendan C. McKiernan

Research output: Contribution to journalArticlepeer-review

Abstract

Objective - To evaluate the bioavailability and pharmacokinetic characteristics of 2 commercially available extended-release theophylline formulations in dogs. Design - Randomized 3-way crossover study. Animals - 6 healthy adult dogs. Procedure - A single dose of aminophylline (11 mg·kg-1 [5 mg·lb-1], IV, equivalent to 8.6 mg of theophylline/kg [3.9 mg·lb-1]) or extended-release theophylline tablets (mean dose, 15.5 mg·kg-1 [7.04 mg·lb-1], PO) or capsules (mean dose, 15.45 mg·kg -1 [7.02 mg·lb-1], PO) was administered to all dogs. Blood samples were obtained at various times for 36 hours after dosing; plasma was separated and immediately frozen. Plasma samples were analyzed by use of fluorescence polarization immunoassay, Results - Administration of theophylline IV best fit a 2-compartment model with rapid distribution followed by slow elimination. Administration of extended-release theophylline tablets and capsules best fit a 1-compartment model with an absorption phase. Mean values for plasma terminal half-life, volume of distribution, and systemic clearance were 8.4 hours, 0.546 L·kg-1, and 0.780 mL·kg1-·min-1, respectively, after IV administration of theophylline. Systemic availability was > 80% for both oral formulations. Computer simulations predicted that extended-release theophylline tablets or capsules administered at a dosage of 10 mg·kg-1 (4.5 mg·lb-1), PO, every 12 hours would maintain plasma concentrations within the desired therapeutic range of 10 to 20 μg·mL-1. Conclusions and Clinical Relevance - Results of these single-dose studies indicated that administration of the specific brand of extended-release theophylline tablets or capsules used in this study at a dosage of 10 mg·kg-1, PO, every 12 hours would maintain plasma concentrations within the desired therapeutic range (10 to 20 μg·mL-1) in healthy dogs.

Original languageEnglish (US)
Pages (from-to)1113-1119
Number of pages7
JournalJournal of the American Veterinary Medical Association
Volume224
Issue number7
DOIs
StatePublished - Apr 1 2004

ASJC Scopus subject areas

  • veterinary(all)

Fingerprint Dive into the research topics of 'Evaluation of the bioavailability and pharmacokinetics of two extended-release theophylline formulations in dogs'. Together they form a unique fingerprint.

Cite this