Absorption properties of two theophylline sustained-release products in smokers

The absorption of theophylline from two commercial products labelled as having sustained-release properties (Theo-dur; Rio-Ethicals; and Euphyllin Retard; Byk-Gulden) was compared with that of a solution of theophylline (Alcophyllin syrup; Propan-Lipworth) in a multiple-dose study in smokers. As regards bioavailability, results for Theo-dur and Euphyllin Retard tables were statistically indistinguishable from that for the standard, but both products showed significantly slower absorption as reflected by longer times to attain peak concentration and lower peak concentrations. Theo-dur exhibits better sustained-release properties than Euphyllin Retard as judged from the peak/trough ratio and the persistence of concentrations from 6 hours to 12 hours after administration. Assuming linear pharmacokinetics and projecting to therapeutic doses, Euphyllin Retard results in much wider fluctuations between peak and trough concentrations (18,9 and 9,8 micrograms/ml) than does Theo-dur (13,8 and 10,2 micrograms/ml), and this product might be more acceptable in smokers if given in an 8-hourly schedule.