Ten healthy volunteers were each given two separate courses of eight doses of theophylline 200 mg as a slow release preparation at 12 hourly intervals. In the first course (regimen 1) the dose was given at 11.00 h and 23.00 h and in the second (regimen 2) at 05.00 h and 17.00 h. Sixty hours after the start of each course, four consecutive trough serum theophylline concentrations were measured. On regimen 1 the trough concentration of theophylline was 6.2 + 2.2 mg/l (mean ± s.d.) at 11.00 h compared with 5.4 ± 1.9 mg/l at 23.00 h (P < 0.01). This circadian variation was abolished during regimen 2 when the mean theophylline concentrations were identical at 5.2 mg/l. The higher trough concentrations after the evening dose on regimen 1 and the loss of circadian variation on regimen 2 may be due to the change in sleep period in relation to the time of dosing.
Information concerning the prescriptions for theophylline preparations for a group of 80 inpatients and 55 outpatients were examined. Slow-release preparations were overwhelmingly preferred. The majority of patients were receiving low daily doses of theophylline or equivalent, and serum drug level monitoring was almost non-existent.
Twenty volunteers aged between 20 and 57 years were given 197 mg of theophylline (as lysine theophylline) by iv infusion over 5 minutes to test the hypothesis that within the adult age range theophylline clearance declines with age. Samples were assayed for theophylline using the EMIT assay and clearance was determined by standard methods. Clearance values were 0.73 ml/min/kg below age 38 years and 0.75 ml/min/kg at and above age 38 years. Multiple regression analysis using age as a continuous variable showed no relationship between age and clearance.
Six healthy volunteers received an iv infusion of 317 mg lysine theophylline (equivalent to 197 mg anhydrous theophylline) in order to calculate theophylline clearance by standard methods. They subsequently received a 20 minute inhalation of nebulised lysine theophylline. Serum and salivary theophylline concentrations were measured and all saliva was collected for the first hour. From these concentrations estimates were made of the distribution of theophylline into the blood and saliva with 40% to 94% identified in the blood. Very high salivary concentrations were reached during the inhalation phase with saliva: serum concentration ratios of between 60 and 1600.
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