Day-Night Differences in Steady-State Theophylline Pharmacokinetics in Asthmatic Children

Abstract

Potential day-night differences of theophylline absorption and disposition were examined in day-active asthmatic children. Theophylline was given orally as TheoDur tablets and Somophyllin-CRT capsules (random crossover) every 12 hr (0700 and 1900), and patients were studied during two consecutive dosing intervals. In addition, patients were studied during the last 24 hr of a 48-hr continuous, intravenous aminophylline infusion. Serum theophylline concentrations were essentially constant during the intravenous infusion for the day and night periods. Thus, day and night clearances were nearly identical. Following oral administration of Somophyllin-CRT or TheoDur, areas under the serum concentration-time curves were greater during the day than the night, with Somophyllin-CRT yielding greater areas than TheoDur for both dosing intervals. Theophylline was absorbed more rapidly during the day than the night, as evidenced by a time to maximum concentration that occurred earlier in the daytime dosing interval. We conclude that theophylline clearance is not characterized by a circadian rhythm and that absorption of theophylline from Somophyllin-CRT and TheoDur is more rapid and complete during the day than the night.

Key Words:

• Asthma
• Chronopharmacology
• theophylline