The influence of codeine, propantheline and metoclopramide on small bowel transit and theophylline absorption from a...

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.