Theophylline steady-state pharmacokinetics: recent concepts and their application in chronotherapy of reactive airway diseases.
With the introduction of sustained-release theophylline formulations for once-daily dosing or for unequally divided twice-daily dosing, comparison with conventional equally divided twice-daily dosing has been focused on nocturnal serum theophylline concentrations (STCs), plateau properties and peak-trough fluctuation. The merits of various steady-state characteristics such as nocturnal excess, plateau time, residual concentration, peak-trough fluctuation, swing and AUC fluctuation are illustrated by 15 data sets from 7 multiple-dose studies, each including either 10-12 healthy volunteers or 12-20 COPD-patients. In all of the studies, STCs were determined at least every 2 hr over a 24-hr period in steady-state. Included in the studies were 7 sustained-release theophylline formulations which were administered either once daily (in the morning or in the evening), or twice daily (either equally divided, or unequally divided with one-third of the dose being given in the morning and two-thirds in the evening.
Steinijans
V W
VW
Byk Gulden Lung Research Center, Konstanz, F.R.G.
Trautmann
H
H
Johnson
E
E
Beier
W
W
D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D006801:Humans; D007700:Kinetics; D008173:Lung Diseases, Obstructive / Q000097:blood / Q000188:drug therapy*; D013806:Theophylline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D013806:Theophylline