Pharmacokinetics of sustained release theophylline in low and high multidose regimens.

1 The 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 5 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 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 (300 mg) resulted on day 6 in a mean serum concentration of 4.4 +/- 0.8 microgram ml-1. The dose of 900 mg resulted in a proportional increase in the serum concentration. The result was 13.3 +/- 2.2 micrograms ml-1. 5 The T1/2 (300 mg) was 9.3 +/- 1.4 h and the T1/2 (900 mg) was 8.5 +/- 2.0 h. These values do not significantly differ (0.10 less than P less than 0.20). 6 It was concluded that theophylline exhibits the rules of linear pharmacokinetics when serum concentrations are in the therapeutic range.