Comparison between steady state pharmacokinetics and effects of two once-daily, slow-release theophylline formulations in nocturnal asthma.
The effects on bronchoconstriction, on non-specific bronchial hyperreactivity (nBH), and the pharmacokinetics at steady state of two theophylline preparations, controlled release (CR) capsules (Riker Pharmaceuticals) and UnixanR tablets (Pharmacia) were compared in patients with nocturnal asthma. Doses were individualised with the intention of achieving plasma trough concentrations greater than 8 micrograms/ml with CR-capsules. The same dose of the two formulations was taken in the morning during two 2-week periods in a randomised, double-blind, cross-over design. During a 24 h hospital study day at the end of the two periods, pulmonary function tests, blood samples, and bronchial histamine challenges were performed. Eleven patients completed the study. Doses were median 15 mg/kg (range 10-20). FEV1 and PEF were statistically significantly better (p less than 0.05) 24 h after dosing (08:00) with CR-capsules. No statistically significant changes in nBH were demonstrated. Despite no significant differences in extents of absorption, the plasma theophylline concentration fluctuations were significantly less (p less than 0.001) during treatment with CR-capsules. We found CR-capsules superior to Unixan in pharmacodynamics 24 h after dosing and in pharmacokinetics with equal bioavailability. In nocturnal asthma the pharmacodynamic differences may be eliminated with evening dosing. No statistically significant changes in nBH were observed.
Nielsen
N H
NH
Medical Dept. TTA, State University Hospital, Copenhagen, Denmark.
Madsen
F
F
Svendsen
U G
UG
Almind
M
M
Frølund
L
L
Weeke
B
B
D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D003692:Delayed-Action Preparations; D013806:Theophylline