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

Jonathan F. Bach Denver Veterinary Specialists, 3695 Kipling St, Wheat Ridge, CO 80033.
Present address is Foster Hospital for Small Animals, School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.

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Butch Kukanich Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

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Mark G. Papich Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

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Brendan C. McKiernan Denver Veterinary Specialists, 3695 Kipling St, Wheat Ridge, CO 80033.

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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·kg–1·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. (J Am Vet Med Assoc 2004;224:1113–1119)

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·kg–1·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. (J Am Vet Med Assoc 2004;224:1113–1119)

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