Steady-state pharmacokinetics and effects of a new once-daily, slow-release theophylline capsule preparation in asthma.

Abstract

Plasma and saliva theophylline concentrations were measured in 21 asthmatic subjects receiving chronic oral therapy with a new sustained-release theophylline capsule (K1B Riker) given as a once daily dose, after titration to achieve a before-dose concentration of 8 mg l-1 or greater, or to the maximum dose of 1200 mg of theophylline daily. Plasma concentrations rose from a mean +/- s.d. minimum concentration (Cmin) of 7.9 +/- 2.3 mg l-1 to a mean maximum of 13.6 +/- 3.3 mg l-1 at a median time of 10 h after dosing. Saliva theophylline concentrations were closely related to the plasma theophylline concentration both between and within subjects with a mean saliva to plasma concentration ratio between subjects (S/P ratio) of 0.62 (+/- 0.05) and a mean within subject coefficient of variation of 8.2% (+/- 4.5%). There was a significant but small (10%) change in the mean S/P ratio during the dosing interval. Peak expiratory flow rate (PEFR) changed slightly but significantly during the dosing interval but forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) did not. The drug was well tolerated at the dose used (600-1200 mg once daily).