Journal of Clinical and Hospirul Pharmacy (1985) zyxwvu 10,211-217. zyxw THEOPHYLLINE VERSUS AMINOPHYLLINE zyx IN RECTAL ADMINISTRATION Elka Touitou and Shimona Yosselson-Superstine School of Pharmacy, Deparrmrnt zyxwvuts of Pharmacy, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91 120, Israel SUMMARY This study was undertaken to compare the bioavailability and the in vitro release rates of theophylline from suppositories containing either theophylline or aminophylline. The absorption of theophylline from solution and from freshly prepared suppositories formulated with Suppocire and containing anhydrous theophylline 250mg or aminophylline 300 mg was investigated in six healthy volunteers in a blind crossover design experiment. Venous blood samples were collected before drug administration and at 1, zyxw 2, 4, 6 and 8 h after- wards. Theophylline serum levels were measured spectrophotometrically. The pharmacokinetic parameters obtained: zyxwv C,,, 6.7 and 5.4 pg ml- zyx ', t,,, 2 h, and zyxwvutsr F,, 0.79 and 0.83 for theophylline and aminophylline, respec- tively, show that the two formulations are almost bioequivalent, with a slightly higher C,,, for theophylline. The in vitro release rate of theophylline from freshly prepared formulations was, however, higher (4.8 mg min- ') from aminophylline suppositories relative to those contain- ing theophylline (2.9 mg min- '). This lack of correlation between the in virro and in wiwo results is explained by the different drug thermodynamic activities in the processes of release and membrane penetration. Thus, a better water-solubility does not automatically point to a better rectal bioavailability. The release rate of aminophylline suppositories tested after 1 -year storage at room temperature dropped from 4.8 to zyxw 0.5 mg min- ' . The bioequivalence of theophylline and aminophylline freshly prepared suppositories and the stability problems associated with fatty-base aminophylline suppositories indicate that the choice of ethylenediamine derivative of theophylline is an empirical development, theoretically unjustified, and must be replaced by theophylline reformulations. INTRO D UCT I0 N Theophylline derivatives are widely used for the treatment of bronchial asthma. By far the most commonly used is the water-soluble combination with ethylenediamine 211