Bioavailability and pharmacological effects of two slow-release theophylline preparations: intrasubject...

The bioavailability and pharmacological effects of slow-release preparations oxtriphylline (Choledyl SA) and anhydrous theophylline (Theo-Dur) were compared in a single-blind, randomized, crossover study in 10 normal men. Subjects were administered three doses from the same lot of each preparation at weekly intervals. Plasma concentration of theophylline was measured at timed intervals for 33 hr by high-pressure liquid chromatography. Pharmacokinetic analysis showed that Choledyl SA peaked earlier (4.7 +/- 1.0 hr) than did Theo-Dur (9.6 +/- 8.2 hr), with higher peak concentrations, 6.4 +/- 0.7 micrograms/ml versus 4.1 +/- 0.5 micrograms/ml for Theo-Dur, and greater are under the curve, 102.4 +/- 15.7 micrograms/ml X hr versus 75.3 +/- 9.1 micrograms/ml X hr for Theo-Dur. 88% absorption was achieved in 6 hr with Choledyl SA versus 10 hr with Theo-Dur. Wide intra- and intersubject variations were observed with both preparations. Likewise, variable effects on systolic and diastolic blood pressure and pulse were observed with both preparations. The effects of both theophylline preparations on urine flow, osmolar clearance, and glomerular filtration rate were compared. Osmotic diuresis without detectable changes in the glomerular filtration rate was observed in subjects who received Choledyl SA versus Theo-Dur. Differences in the bioavailability and renal effects were observed between Choledyl SA and Theo-Dur. Wide intra- and intersubject tablet-to-tablet variability were observed with both preparations.