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PHARMACODYNAMIC EFFECTS OF ORAL THEOPHYLLINE IN APPARENTLY HEALTHY DOGS
Thesis

PHARMACODYNAMIC EFFECTS OF ORAL THEOPHYLLINE IN APPARENTLY HEALTHY DOGS

Anna Alicia Golden
Master of Science (MS), Washington State University
2026
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Abstract

Cardiology Veterinary Medicine
Background: Theophylline is used as a positive chronotropic agent in dogs, but dose-response data are limited.Hypothesis/Objectives: To determine whether oral theophylline produces dose-dependent changes in heart rate and heart rate variability (HRV). Animals: Ten healthy client-owned dogs. Materials and methods: Randomized, double-blinded, crossover study. Dogs received modified compounded theophylline at 5 or 10 mg/kg orally every 12 hours for 7 days, separated by a ≥14-day washout. Forty-eight-hour Holter monitoring was performed at baseline and during treatment. Primary outcomes were 24-hour heart rate indices and HRV variables. Results: Compared with baseline, maximum heart rate increased at 5 mg/kg (mean difference, +25.7 beats/min; 95% CI, 3.0-48.4; P = .030) and 10 mg/kg (+29.0 beats/min; 95% CI, 10.3-47.7; P = .007). Average heart rate increased at 10 mg/kg (+8.6 beats/min; 95% CI, 2.6-14.6; P = .010) but not at 5 mg/kg. Minimum heart rate, pause burden, and arrhythmia burden did not differ. Time-domain HRV indices decreased, most consistently at 10 mg/kg (SDNN, -0.059 s; 95% CI, 0.026-0.092; P = .003; RMSSD, -0.074 s; 95% CI, 0.022-0.125; P = .010). Serum concentrations were 9.86 ± 3.75 and 17.98 ± 4.97 µg/mL at 5 and 10 mg/kg. Conclusions and clinical importance: Oral theophylline produced dose-associated chronotropic effects and reduced HRV without increasing arrhythmia burden in healthy dogs. Findings support rational dose selection and future evaluation in dogs with bradyarrhythmias.

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