The effect of dosing time on the pharmacokinetics and pharmacodynamics of a ‘once‐a‐day’ sustained release theophylline preparation.

1. The pharmacokinetics and the bronchodilating effect of theophylline were studied during 1 week of morning dosing and 1 week of evening dosing in a randomized cross‐over design in thirteen patients with reversible airways obstruction, treated with a new ‘once‐a‐day’ theophylline capsule formulation. 2. There were no differences between the mean pre‐dose trough plasma concentration, maximal plasma concentration, trough‐to‐peak variation, tmax, area under the plasma drug concentration time‐curve after morning or evening dosage. There was only a slightly but significantly higher plasma theophylline concentration between 16 and 20 h after evening dosing. 3. The mean plasma drug concentration time‐curves were relatively flat with a mean trough to peak variation of 73.9% after morning dosing and 66.7% after evening dosing. Both sets of mean data were within the 10‐20 mg l‐1 therapeutic range. 4. The variations in FEV1 and PEFR throughout the 24 h after either morning or evening dosing were similar and followed the normal pattern of diurnal variation. 5. Adverse effects were mild and occurred in three patients without causing discontinuation of the study. 6. The theophylline preparation used appears suitable for once a day administration either in the morning or in the evening.

DOI: 10.1111/j.1365-2125.1987.tb03239.x

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