The pharmacokinetics of theophylline (Uniphyllin) in blood and saliva was compared after morning and evening administration of a once-daily dose in a randomized cross-over study. Ten bronchial asthma patients received multiple doses of 800 mg theophylline at 8 a.m. and 8 p.m. under controlled food conditions. The precision of the serum concentration prediction from salivary measurements in individual patients was sufficient to obtain identical pharmacokinetic parameters and parallel concentration-time curves. There were no significant differences in the values of mean residence time and area under the concentration-time curves after morning and evening dosing, either in the kinetics of elimination and in the volume of distribution. The fluctuation of concentrations during the dosing intervals was 100% after morning doses and 80% after evening doses. No consistent interference with food was found. Circadian variation in the kinetics of drug disposition after once-daily theophylline administration did not occur. In order to achieve higher therapeutical levels at night and in the morning, the evening dosing seems to be preferable.

State Institute for Drug Control Prague Czechoslovakia