Evaluation of the bioavailability and pharmacokinetics of two extended-release theophylline formulations in dogs.
OBJECTIVE
To evaluate the bioavailability and pharmacokinetic characteristics of 2 commercially available extended-release theophylline formulations in dogs.


METHODS
Randomized 3-way crossover study.


METHODS
6 healthy adult dogs.


METHODS
A single dose of aminophylline (11 mg x kg(-1) 15 mg x lb(-1)], i.v., equivalent to 8.6 mg of theophylline/kg 13.9 mg x lb(-1) or extended-release theophylline tablets (mean dose, 15.5 mg x kg(-1) [7.04 mg x lb9-1), PO) or capsules (mean dose, 15.45 mg x kg(-1) [7.02 mg x 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 i.v. 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 x kg(-1), and 0.780 mL x kg(-1) x min(1), respectively, after i.v. 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 x kg(-1) (4.5 mg x lb(-1)), PO, every 12 hours would maintain plasma concentrations within the desired therapeutic range of 10 to 20 microg x mL(-10.


CONCLUSIONS
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 x kg(-1), PO, every 12 hours would maintain plasma concentrations within the desired therapeutic range (10 to 20 microg x mL(-1)) in healthy dogs.
Bach
Jonathan E
JE
Denver Veterinary Specialists, 3695 Kipling St, Wheat Ridge, CO 80033, USA.
Kukanich
Butch
B
Papich
Mark G
MG
McKiernan
Brendan C
BC
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002214:Capsules; D003198:Computer Simulation; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004285:Dogs / Q000097:blood / Q000378:metabolism*; D004334:Drug Administration Schedule / Q000662:veterinary; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D011897:Random Allocation; D013607:Tablets; D013806:Theophylline / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
D001993:Bronchodilator Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D013607:Tablets; D013806:Theophylline