The Influence of Codeine, Propantheline and Metoclopramide on Small Bowel Transit and Theophylline Absorption from a Sustained-release Formulation

1. The effects of the anticholinergic agent, propantheline, the opiate, codeine, and the prokinetic agent, metoclopramide, on oral-caecal transit time and on the absorption of theophylline from a sustained-release formulation were examined in six healthy male volunteers. 2. A cross-over randomised sequence design was followed, allowing at least 2 weeks interval between studies. On each occasion 500 mg theophylline in a sustained-release formulation was taken simultaneously with 2 g sulphasalazine at zero time. On three of the four occasions one of the following treatments was given concurrently at -0.5 h, +3.5 h, and +7.5 h: 30 mg codeine phosphate, 30 mg propantheline bromide, or 10 mg metoclopramide monohydrochloride. 3. The appearance of sulphapyridine in the plasma was used to assess oral-caecal transit time and the mean fraction absorbed-time profile of theophylline was calculated from serial serum theophylline concentration measurements using the Wagner-Nelson method. 4. Codeine increased the mean (s.d.) oral-caecal time (h) significantly (5.14 +/- 0.94) compared with the control value (3.78 +/- 0.34). Propantheline inhibited peristaltic contractions to such an extent that the oral-caecal transit time in five of the volunteers was between 9 and 25 h, while sulphapyridine appeared in the 9 h serum sample of the sixth. Metoclopramide did not significantly alter the oral-caecal transit time. 5. Despite the observed changes in oral-caecal transit time the rate and extent of theophylline absorption was similar with all regimens.