Evaluation of the absorption from some commercial enteric-release theophylline products.
In a single-dose bioavailability study, Wales, Robinson, Columbia, and Choledyl (Warner/Chilcott) enteric-coated tablets all allowed a bioavailability of theophylline (99% +/- 25%, 102% +/- 23%, 103% +/- 18%, and 98% +/- 15%; mean +/- SD, n = 12) statistically indistinguishable from that of the standard uncoated tablet (Searle 200 mg aminophylline). Only the Wales and Choledyl tablets (7.6, 4.2 hr) could be shown (p < 0.5) to generate a peak plasma theophylline concentration later than the standard (1.4 hr). All tablet brands demonstrated a significant lag time before appearance of theophylline in the plasma, and both Wales and Choledyl tablets also had a (tpeak-tlag) statistically different from that of the standard. Despite misleading indications from the mean plasma profile (plasma concentrations at each sampling time averaged over all subjects), plasma data from the individual participants and in vitro dissolution data show that, while release of theophylline from the Wales tablet might be inordinately slow, this is not a sustained-release preparation. Of the enteric-coated tablets only the Columbia product allowed significant levels in the first sample after dosage. Five of the 18 Columbia doses gave rise to 40-99% of the peak concentration in the 1-hr sample. In vitro, it takes 39 +/- 14 min for 40% of the theophylline content of Columbia tablets to dissolve in simulated intestinal fluid. Suprisingly rapid delivery of an enteric-coated tablet to the duodenum would appear to be required to allow a significant percentage of theophylline to be dissolved and absorbed before 1 hr. None of 12 Columbia tablets tested in vitro, however, allowed dissolution of more than 1.2% of their theophylline content during 1 hr immersion in simulated gastric fluid. Since once in intestinal fluid Columbia tablets appear to dissolve more rapidly than the other enteric products, it is not clear whether the five Columbia tablets in question had imperfections or wheter, in fact, this tablet brand more closely than the others represents the ideal of immediate release once in the duodenum. Plasma samples should be taken as early as 15 min after dosage when evaluating the bioavailability of enteric release products.
D000328:Adult; D001682:Biological Availability; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D013608:Tablets, Enteric-Coated; D013806:Theophylline / Q000008:administration & dosage / Q000378:metabolism*
D013608:Tablets, Enteric-Coated; D013806:Theophylline