Objective—To evaluate the bioavailability and pharmacokinetic
characteristics of 2 commercially available
extended-release theophylline formulations in
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
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)
Objective—To evaluate the effects of obesity on pulmonary function in healthy adult dogs.
Animals—36 Retrievers without cardiopulmonary disease.
Procedures—Dogs were assigned to 1 of 3 groups on the basis of body condition score (1 through 9): nonobese (score, 4.5 to 5.5), moderately obese (score, 6.0 to 6.5), and markedly obese (score, 7.0 to 9.0). Pulmonary function tests performed in conscious dogs included spirometry and measurement of inspiratory and expiratory airway resistance (Raw) and specific Raw (sRaw) during normal breathing and during hyperpnea via head-out whole-body plethysmography. Functional residual capacity (FRC; measured by use of helium dilution), diffusion capacity of lungs for carbon monoxide (DLCO), and arterial blood gas variables (PaO2, PaCO2, and alveolar-arterial gradient) were assessed.
Results—During normal breathing, body condition score did not influence airway function, DLCO, or arterial blood gas variables. During hyperpnea, expiratory sRaw was significantly greater in markedly obese dogs than nonobese dogs and Raw was significantly greater in markedly obese dogs, compared with nonobese and moderately obese dogs. Although not significantly different, markedly obese dogs had a somewhat lower FRC, compared with other dogs.
Conclusions and Clinical Relevance—In dogs, obesity appeared to cause airflow limitation during the expiratory phase of breathing, but this was only evident during hyperpnea. This suggests that flow limitation is dynamic and likely occurs in the distal (rather than proximal) portions of the airways. Further studies are warranted to localize the flow-limited segment and understand whether obesity is linked to exercise intolerance via airway dys-function in dogs.