PHARMACOKINETIC CHARACTERISTICS OF A NEW LIQUID SUSTAINED-RELEASE FORMULATION OF THEOPHYLLINE DESIGNED FOR THE ELDERLY AND CHILDREN - MICROCAPS AS SACHET

A new sustained-release theophylline formulation was especially design ed for the elderly and children. Microcapsules of theophylline, admini stered as a suspension in water, proved to be a suitable dosage form f or a clientele with impaired or difficult deglutition. Pharmacokinetic characteristics of 2 batches at the lower (T-1) and upper (T-2) in vi tro dissolution specification range of this new formulation and a pell et formulation (R) as a comparator were evaluated in an open, randomiz ed, 3-way, multiple-dose, crossover study design with an asymmetric do sage regimen of 400 mg and 200 mg theophylline. Smooth and safe plasma concentrations with a high and long-lasting plateau were achieved wit h this new formulation. Plateau times which are independent of the asy mmetric dosage regimen ranged from 16.4 hours (T-1) to 13.8 hours (T-2 ) and could therefore span sufficient time of the dosage interval. Max imum serum levels of 9.6 mu g/ml and 10.0 mu g/ml were attained 6.6 an d 6.1 hours after dosing of T-1 and T-2, coinciding perfectly with the time of the critical morning dip at 2 - 4 a.m. With a nocturnal exces s of 15.5% (T-1) and 17.9% (T-2) this circadian-tailored asymmetric do sage regimen proved to take into account the chronopathology of asthma and the chronopharmacokinetics of theophylline sustained-release prep arations. Bioequivalence of all 3 formulations versus each other with regard to rate (C-max(ss)) and extent (AUC(tau)(ss)) of absorption cou ld be established for the 2 batches at the upper and lower in vitro sp ecification range and for both batches of the new formulation compared to the reference, All in all, safety and efficacy of this new liquid prolonged-release theophylline could be established. Furthermore, in v itro specifications could be justified according to current EU guideli nes.