ABSORPTION PROFILE AND ABSOLUTE BIOAVAILABILITY OF A THEOPHYLLINE SUSTAINED-RELEASE PREPARATION

In a single-dose crossover study with 16 healthy male nonsmoking volun teers the absorption profile and absolute bioavailability of the susta ined release pellets contained in all dosage strengths of Bronchoretar d(R) (100, 200, 350, 500 mg anhydrous theophylline) were investigated. One capsule (500 mg theophylline) was given after an evening meal. Th e reference treatment consisted of an i.v. infusion over 8 h in a tota l dosage of 350 mg theophylline. Plasma concentration-time profiles we re evaluated for 72 h after dosing, respectively start of infusion. Th eophylline was measured by high-performance liquid chromatography (HPL C). Absorption profiles (Wagner-Nelson) were derived and the absolute bioavailability was calculated. For the sustained release pellets a li beration/absorption of zero order for 12 h could be noted; the dose-co rrected mean absolute bioavailability was 88 %. The assumptions of an investigation on absolute bioavailability are discussed and the limita tions on generalizability resulting therefrom.