[Pharmacokinetics of a theophylline sustained-release formulation after single and twice daily dosage]

Sustained release theophylline (CAS 58-55-9) preparations may be dosed once or alternatively twice-a-day, depending on the intention of a theophylline therapy. A once-a-day dosage regimen is considered appropriate in patients with nocturnal asthma attacks, whereas a twice-a-day regimen is advantageous for guaranteeing bronchodilatation and to control the underlying inflammatory disease. Therefore, pharmacokinetic characteristics of both modes of administration were evaluated in a randomised, two-way crossover study in 18 female and male elderly volunteers under multiple-dose conditions. The shape of the pharmacokinetic profiles showed the expected and pronounced differences, while the extent of absorption was bioequivalent. Twice daily administration decreased the nocturnal maximum concentration and at the same time increased the minimum concentration. At the expense of the nocturnal excess, the peak-trough fluctuations (PTF) were reduced from 92.1% to 39.5%. Plateau times of 11.4 h and 20.2 h were achieved with both modes of administration. As for theophylline with its narrow therapeutic range, high quality sustained release preparations distinguish themselves by long plateau times and small peak-trough fluctuations such as those observed with the preparation under investigation. When using this preparation, therapeutic concentrations necessary for safety and efficacy are assured under either a once- or a twice-daily dosing regimen.