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1The in vitro characteristics (dissolution rate) of a sustained release theophylline preparation (Theo-Dur®) were first measured in acid medium (pH = 1) for 2 h and after that in a phosphate buffer (pH = 6.8) for 6 h. 2 The tablets released more than 95% of the active ingredient within 6 h at a rate of approximately 11% of the dose per hour at pH = 1 and about 18% at pH = 6.8. 3 Dose dependency of the pharmacokinetics of theophylline was tested in seven healthy volunteers by giving them either 300 mg Theo-Dur(E) or 900 mg Theo-Dur® in two doses a day for 5 days in a cross over design. After the last tablet on day 6 the fall-off curve was followed in order to calculate the pharmacokinetic parameters. 4 Theophylline (300mg) resulted on day 6 in a mean serum concentration of 4.4 0.8 ,ug ml-'The dose of 900 mg resulted in a proportional increase in the serum concentration. The result was 13.3 + 2.2 g ml-'. 5The T½,2 (300 mg) was 9.3 + 1.4 h and the 7T/2 (900 mg) was 8.5 + 2.0 h. These values do not significantly differ (0.10 < P < 0.20). 6 It was concluded that theophylline exhibits the rules of linear pharmacokinetics when serum concentrations are in the therapeutic range.

The correlation between serum and saliva levels of theophylline was investigated in seven healthy volunteers after multiple dose administration of a low dose (300 mg/day) and a high dose (900 mg/day) of a sustained release theophylline preparation (Theo-Dur). Tablets were taken for five days, at 8 a. m. and 8 p. m. and a last dose was taken on Day 6 at 8 a. m. Fourteen serum and saliva samples were collected simultaneously during the dosing period and for up to 32 h after the last dose. On the 300 mg/day regimen the level in saliva was 55.3% of the serum level, with an overall variability of 6.7% and an intrasubject variability of 10.5%. After 900 mg/day, the saliva concentration was 55.5% of the serum concentration, with an overall variability of 7.6% and an intrasubject variability of 12.7%. A good correlation was found between both determinations (r = 0.99), which suggests that saliva levels could be used to monitor theophylline after administration of a sustained release tablet.

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