| Abstract: | The temporal variation in trough (i.e., predose) theophylline concentrations at steady state was examined. In general, adult subjects dosed with solid theophylline formulations have morning trough theophylline concentrations 10-16% greater than corresponding evening troughs; this morning-to-evening drop is statistically significant. Large-percentage diurnal changes (greater than +/- 20% and even greater than or equal to +/- 40%) in trough-to-trough serum theophylline concentrations are not uncommon in adults. However, the change in absolute trough theophylline concentrations is pronounced in only some individuals. Repetitive studies in four of five individuals tested generally demonstrated within-individual reproducibility in the direction (but not magnitude) of the temporal variation in trough theophylline concentration. This finding further substantiates the morning-to-evening change in trough theophylline concentration as a real phenomenon and not merely the result of random variability. It is believed that the temporal variability in trough concentration observed after peroral theophylline administration requires monitoring theophylline dosage needs by obtaining blood samples at the same time each day. |
