Disposition and clinical pharmacokinetics of theophylline after administration of a new sustained release tablet

Summary

The systemic disposition of theophylline after taking a new, sustained release tablet (Theolair Retard^® 250 mg, Theolair S. R.^®, Riker Laboratories) has been studied in 8 hospitalized patients. Absolute bioavailability was determined from the ratios of the areas under the serum concentration-time curves after intake of the tablet and after intravenous infusion of aminophylline in the same patient. The absolute bioavailability of Theolair Retard^® 250 mg was 110.9±20.8% (mean ± SD). Maximal serum concentrations were reached after 7.3±3.5 h, the large intersubject variation being due to differences in gastric emptying time. The tablets appear to release theophylline slowly in acid conditions, but more rapidly in an alkaline medium. Invasion was found to be either monophasic with a rate constant of about 0.8 h⁻¹ (intestine), or biphasic with rate constants of 0.2 h⁻¹ (stomach) and 0.8 h⁻¹ (intestine). The peak levels accounted for 7.9±2.2 mg · 1⁻¹. The profiles of the serum concentration-time curves were such that the concentrations remained above 80% of c^max for 6.5±3.3 h. The relevant pharmacokinetic parameters (half-life of elimination, total body clearance and volume of distribution) were determined and were used to calculate the individual dosage regimens required to obtain therapeutic serum concentrations. The optimal dosing interval to obtain an average steady state serum concentration of 12.5 mg · l⁻¹ was 9.8±3.1 h.