Chronopharmacokinetics of theophylline in the cat

Studies of theophylline pharmacokinetics in humans have shown that a higher peak concentration and area under the curve (AUC), with a shorter time to peak (tp) occur after a morning dose than after an evening dose. The purpose of this study was to determine whether theophylline pharmacokinetics in the cat were also influenced by the administration time of day. Theophylline was administered to six cats in a three-way cross-over study as a single dose of intravenous aminophylline and oral sustained-release theophylline (Slo-bid Gyrocaps and Theo-Dur Tablets), between 08.00-09.00 h (Phase I) and 20.00-21.00 h (Phase II). Subjects were maintained on a 12-h light (08.00-20.00 h): 12-h dark cycle. Similar to the human studies, the tp was shorter following the morning dose. Conversely, however, the peak plasma theophylline concentrations achieved in these cats following intravenous aminophylline and oral Slo-bid were significantly higher following the evening dose. The AUC obtained for Theo-Dur was also significantly greater following the evening dose. No single pharmacokinetic parameter could account for the higher plasma concentrations achieved following the evening dose.