Serum theophylline levels after use of an anhydrous crystalline theophylline suppository.

The absorption of theophylline from a suppository not containing ethylenediamine was tested in 9 healthy volunteers. AUC after rectal administration of anhydrous crystalline theophylline 250 mg (AUCrectal) was compared with the AUC after oral administration of microcrystalline theophylline 250 mg (Nuelin; AUCoral) in a randomized, cross-over study. The ratio AUCrectal/AUCoral was 0.75 at 10h, and the ratio AUCrectal x beta rectal/AUCoral x beta oral extrapolated to infinite time was 0.83. A mean concentration of 5.7 micrograms/ml was reached 3.7 h after a single rectal dose. The absorption studied were performed with suppositories stored for 15 weeks at 22 degrees C. No effect on the in vitro release rate of theophylline from the suppository was observed during storage at room temperature from 3 to 31 weeks after production. Since aminophylline suppositories are known to decompose upon storage, the results suggest that a formulation without ethylenediamine is preferable for the rectal administration of theophylline.