Comparative bio-availability of theophylline whole and halved sustained-release tablets

In a randomised, multiple-dose, cross-over study in 14 healthy volunteers, plasma theophylline concentrations were compared during a 12-hour dosing interval after repeated administration of theophylline (Euphyllin Retard; Byk Gulden) as whole and halved tablets. Bio-availability of theophylline from the halved tablets relative to the whole tablets was: 116% (100%, 134%) for the extent of absorption as judged by the area under the concentration time curve (AUC) and 115% (99%, 135%) for the rate of absorption as judged by maximum concentration (Cmax). The confidence levels for the 80-120% bio-equivalence range were 72% (AUC) and 76% (Cmax), those for the 80 and 125% range were 91% (AUC) and 91% (Cmax). The plateau times T75% Cmax, which characterise the sustained-released properties, were 8.5 +/- 2.9 hours (halved) and 8.3 +/- 2.5 hours (whole) during the 12-hour dosing interval. It is concluded that no clinically relevant deviations in steady-state plasma theophylline concentration and sustained-release properties are likely to result from breaking (halving) the film-coated tablets.