The pharmacokinetics of a new sustained-release preparation of theophylline (Dilatrane à Action Prolongée capsules filled with homogenous microgranules) has been after its studied administration to 7 healthy volunteers at 8 p.m. in order to achieve therapeutic levels at night and in the morning. In separate trials the test dose of 500 or 600 mg was administered for 7 days, once daily at 8 p.m. Plasma theophylline levels were measured by capillary gas chromatography with a mass specific detector after pentylation, using internal standards labelled with stable isotopes (
15N-1,3 and
13C-2 theophylline). The new sustained-release preparation showed a monophasic regular absorption phase with very low interindividual variability. After administration, the plasma level stayed within 80% of the peak levels for 8.5±1.5 h. There was a good correlation between the dose and the steady state plasma level (
r=0.9587;
p<0.05). this="" preparation="" can="" be="" chronically="" administered="" once="" daily="" day="" at="" 8="" p.m.="" in="" order="" to="" achieve="" a="" therapeutic="" level="" during="" the="" night="" and="" the="" morning,="" and="" to="" provide="" sufficient="" protection="" during="" the="" nycterohemeral="" period,="" with="" a="" once="" dose="" a="" day="">0.05).>
Key words theophylline - sustained release - pharmacokinetics - chronic administration - healthy volunteers - plasma levels - GCMS assay - stable isotope technique