Circadian variation in theophylline absorption during chronic dosing with a slow release theophylline preparation and the effect of clock time of dosing.
1. Eight volunteers were given seven doses of 200 mg of slow release theophylline at either 11.00 h and 23.00 h (regimen 1) or 17.00 h and 05.00 h (regimen 2). At the time of the sixth dose (60 h) hourly blood sampling was started and continued for 24 h. After at least 1 week volunteers crossed over to the other regimen. 2. Volunteers retired to bed at 23.00 h and arose after the 07.00 h sample during both regimens. 3. During regimen 1 there was a marked rise in mean tmax from 3.3 h after dosing at 11.00 h to 9.3 h after dosing at 23.00 h (P less than 0.001). There was also a fall in AUC(0,12) from 89.9 mg l-1 h after dosing at 11.00 h to 79.0 mg l-1 h after dosing at 23.00 h. There was no difference in mean Cmax values. 4. During regimen 2 these circadian changes were abolished with mean values after both dosing times lying between those observed during regimen 1. 5. A marked delay in absorption occurs at night and cannot be explained by food intake.
Jackson
S H
SH
Department of Clinical Pharmacology, St Bartholomew's Hospital, London.
Johnston
A
A
Woollard
R
R
Abrams
S M
SM
Turner
P
P
D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D013806:Theophylline