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

Abstract

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-aday' 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 1-1 therapeutic range. 4 The variations in FEV, 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.