IN-VIVO VERIFICATION OF THE IN-VITRO RELEASE SPECIFICATION OF A SUSTAINED-RELEASE THEOPHYLLINE PREPARATION

Especially in drugs with a narrow therapeutic range, ''within product bioequivalence'' i.e. ''batch-to-batch bioequivalence'' should be scru tinized. Therefore, pharmacokinetics and bioavailability of two batche s at the upper and lower in vitro specification range as well as a bat ch representing the middle of the specification range was evaluated in an in vivo bioequivalence study. An open, randomized, 3-way crossover , multiple dose study in 18 healthy, male volunteers was selected for this purpose. Bioequivalence regarding rate (C-max ss; t75%C-max) and extent (AUC(ss)) of absorption could be established for both extreme b atches at the lower and upper in vitro specification range. Additional ly both batches proved to be bioequivalent compared to the batch in th e middle of the in vitro specification range. As a result, reproducibl e concentration-time profiles can be guaranteed for all batches of thi s sustained release theophylline (CAS 58-55-9) preparation. Furthermor e, pharmacokinetic characteristics of all three batches meet the quali ty criteria defined for sustained release theophylline preparations, g uaranteeing optimal concentration/time profiles for the therapy of ast hma.