Time‐Dependent Absorption of Theophylline in Man

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Abstract
Sixteen healthy volunteers were given either oral or intravenous doses of aminophylline (125 mg) at 9:00 a.m. and 9:00 p.m. under controlled food conditions. Measured at regular time intervals by homogeneous enzyme immunoassay, the plasma theophylline concentrations 1.5 and 2 hours after oral aminophylline were significantly higher in the morning than in the evening (P < 0.05). Also, the mean peak plasma concentration was significantly higher (P < 0.05) and the time to peak concentration was faster (P = 0.02) after the morning dose. Neither the morning mean elimination half-life nor the morning mean area under the plasma concentration-time curve differed significantly from those after the evening dose. After intravenous aminophylline, no significant differences were found in the plasma theophylline concentrations and in the elimination half-life between morning and evening. Therefore, the small but statistically significant time-dependent differences in theophylline kinetics must be due to changes in absorption from the gastrointestinal tract and not to changes in distribution or elimination of the drug.

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