Bioavailability and efficacy of a sustained‐release theophylline tablet

To determine bioavailability of theophylline in a new dosage form, plasma drug concentration time curves were observed in 5 normal male sub;ects after an intravenous dose of 4 mg per kilogram and after an oral dose of 700 mg as 2 oral tablets. Using kinetic parameters derived from the intravenous study, the mean oral absorption rate constant was calculated to be 0.316 ± 0.042 hr‐l with an absorption half‐time of 2.2 hr. Peak concentrations of 9 mg/l (range 7.9 to 11.7) and concentrations greater than 5 mg/l were observed from 2 to 14 hours after an oral dose. The absolute bioavailability of the oral dosage was 77.1 ± 5.4%. One 350 mg tablet every 12 hours was compared with placebo in a double‐blind Latin square trial in 10 sub;ects with intrinsic bronchial asthma. During active drug therapy, the mean observed theophylline concentration of 11.6 mg/l was associated with a 11.2 ± 2.4% improvement in vital capacity and a 13.0 ± 2.9% improvement in forced eXpiratory volume. It is concluded that this oral theophylline preparation will prOVide therapeutic drug concentrations on a 12 hr dose schedule.