PHARMACOKINETICS OF A SUSTAINED-RELEASE THEOPHYLLINE PREPARATION FOLLOWING ONCE-A-DAY AND TWICE-A-DAY MULTIPLE DOSING

Sustained release theophylline (CAS 58-55-9) preparations may be dosed once or alternatively twice-a-day, depending on the intention of a th eophylline therapy. A once-a-day dosage regimen is considered appropri ate in patients with nocturnal asthma attacks, whereas a twice-a-day r egimen is advantageous for guaranteeing bronchodilatation and to contr ol the underlying inflammatory disease. Therefore, pharmacokinetic cha racteristics of both modes of administration were evaluated in a rando mised, two-way crossover study in 18 female and male elderly volunteer s under multiple-dose conditions. The shape of the pharmacokinetic pro files 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 th e minimum concentration. At the expense of the nocturnal excess, the p eak-trough fluctuations (PTF) were reduced from 92.1 % to 39.5 %. Plat eau times of 11.4 h and 20.2 h were achieved with both modes of admini stration. 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 observe d with the preparation under investigation. When using this preparatio n, therapeutic concentrations necessary for safety and efficacy are as sured under either a once-or a twice-daily dosing regimen.