Pharmacodynamic Interactions Between Infused Adenosine and Oral Theophylline

Abstract

1 Five healthy human subjects were given, in single-blind fashion, either (a) 625 mg theophylline orally, followed 4 h later, by a 40 min infusion of adenosine (40 μg kg ^-1 min^-1 for 5 min, 60 μg kg^-1 min ^-1 for 5 min and 80 μg kg^-1 min^-1 for 30 min), or (b) 625 mg theophylline orally followed by 0.9% sodium chloride infusion, or (c) placebo theophylline tablets followed by adenosine infusion.

2 All five subjects experienced adverse effects during adenosine infusion, mainly at the higher infusion rates; two subjects also experienced chest pain but not during combined treatment with theophylline and adenosine.

3 Diastolic blood pressure (DBP) rose by 16.5 mmHg (P < 0.001) following treatment with theophylline only, fell by 24.5 mmHg (P < 0.001) during the adenosine infusion after placebo theophylline and remained unchanged during the adenosine infusion following theophylline. Pulse rate rose by 12 min ^-1 (P < 0.01) during adenosine infusion following placebo, but not after theophylline alone or theophylline and adenosine combined.

4 The respiratory rate fell by 6 min^-1 (P < 0.01) during treatment with adenosine only, being lower than for the two treatments containing theophylline (P < 0.05).

5 Plasma potassium and magnesium fell by 0.25 mmol I^-1 (P < 0.001) and 0.037 mmol I^-1 (P < 0.05), respectively, during treatment with theophylline only, but these effects were not altered by infusion of adenosine.

6 This study has demonstrated interactions between theophylline and adenosine on diastolic blood pressure and respiratory rate, but no interaction on metabolic parameters. Adenosine infusion is unlikely to be of value in the management of theophylline toxicity, but its effects on theophylline-induced cardiac arrhythmias remain unexplored.