BIOAVAILABILITY OF THEOPHYLLINE FROM A SUSTAINED-RELEASE AMINOPHYLLINE FORMULATION (EUPHYLLIN RETARD TABLETS) - PLASMA-LEVELS AFTER SINGLE AND MULTIPLE ORAL DOSES

  • 1 January 1981
    • journal article
    • research article
    • Vol. 19  (5) , 223-227
Abstract
Theophylline is used to control chronic asthma. The absolute bioavailability of theophylline in 2 commercially available preparations of aminophylline, a sustained-release formulation (Euphyllin retard tablets) and a solution (Euphyllin solution), was determined in 8 healthy volunteers following oral administration of a single dose. Percent bioavailability was obtained by comparing AUC [area under the concentration time curve] data for theophylline concentration-time curves measured over 24 h with corresponding data following i.v. doses of theophylline. Absorption of theophylline from solution was rapid and complete. Bioavailability amounted to 111 .+-. 16% (.hivin.X [mean] .+-. SD) compared to i.v. administration. Absorption from the sustained-release tablet appeared more erratic and less complete: the time of peak theophylline concentration varied between 2-14 h. The mean plasma level curve showed a plateau between 2-14 h, indicating prolonged absorption of drug. The absolute bioavailability was 83 .+-. 9%; up to 24 h bioavailability was 72 .+-. 13%. The sustained-release formulation was administered twice daily (350 mg) for 4 days. Plasma concentrations during multiple dosing of the sustained release formulation were with 1 exception below 10 mg/l. On day 4 at steady state, peak theophylline concentrations were 8.1 .+-. 0.63 mg/l, trough levels 6.2 .+-. 1.4 mg/l in the morning and 5.6 .+-. 0.67 mg/l in the evening.