Effect of intravenous isoproterenol on theophylline kinetics

Aminophylline and isoproterenol were simultaneously administered by continuous intravenous infusion to six patients with status asthmaticus and acute respiratory failure. During the isoproterenol administration, an increased theophylline clearance was seen in each patient, with a decrease in clearance after the cessation of the isoproterenol infusion. Arterial pH determination during this study did not correlate with the changes in theophylline clearance. Two patients treated with mechanical ventilation for acute respiratory failure secondary to status asthmaticus did not demonstrate the changes in theophylline clearance seen in the patients treated with intravenous isoproterenol. Parallel studies done in four mongrel dogs indicated similar results to those noted in patients. In the dogs, urinary theophylline clearances were also measured during the administration of isoproterenol without any detectable change. These observations suggest a significant, previously unreported drug interaction between theophylline and isoproterenol during their simultaneous intravenous administration. Questions regarding the mechanism of the drug interaction and the therapeutic implications of these findings are also raised.