Quantitative, noninvasive assessment of antidiarrheal actions of codeine using an experimental model of diarrhea in man

Abstract

Enteric coating of a capsule has been used to deliver a bolus of radioisotope to the ileocecal region. This has allowed quantitative assessment of regional colonic transit in a group of healthy subjects whose proximal colonic transit was accelerated by lactulose 20 ml thrice daily. In this experimental model of diarrhea, codeine delayed transit from mouth to terminal ileum and also delayed transit through the ascending colon from 5.3 +/- 2.5 hr to 7.4 +/- 2.5 hr, N = 11, P < 0.05. Furthermore, codeine delayed whole colon transit, as assessed by geometric center analysis, which showed the delay to be most marked in the right colon with little effect noted in the left colon. In addition, codeine significantly reduced the number of retrograde movements observed and reduced the colonic response to eating. The antidiarrheal effect of codeine appears to be due to a combination of delayed mouth-cecum transit plus an additional delay in the ascending colon. This colonic delay may be partially explained by a reduction in postprandial propulsive movements that were seen in this model of diarrhea.

A randomised, placebo‐controlled trial comparing the effects of tapentadol and oxycodone on gastrointestinal and colonic transit in healthy humans

“…Barrow et al . had previously observed that the effect of codeine in human colon was predominantly observed in the ascending colon, with little effect in the left colon . Differential effects of chronically administered mu‐opiate have also been observed in studies of morphine tolerance in the mouse ileum and colon …”

Limited exposure of the healthy distal colon to orally‐dosed formulation is further exaggerated in active left‐sided ulcerative colitis

“…The total radiation dose to subjects was therefore less than 0.9 mSv. All gelatine capsules were given a single coating of Eudragit S100 (Rohm GmbH, Darmstadt, Germany) dissolved in a mixture of 13% w/v isopropyl alcohol/acetone, as our previous experience showed that this resulted in consistent release in the region of the ileo‐caecal junction 9 . Anterior and posterior images of the volunteers were then recorded immediately before the 4th day dose (09.00 hours, scan 1) and at 4, 8 and 12 h afterwards (scans 2, 3 and 4, respectively).…”

The transit of dosage forms through the colon

“…Finally, we attempted to simulate an acute diarrhoeal episode by consumption of lactulose and to reverse the symptoms with codeine (Barrow et al, 1993). Co-administration of [ 111 In]-labelled 0.2 mm Amberlite resin with [ 99m Tc]-labelled Amberlite ® resin 5 mm tablets within an enteric coated tablet that broke up at the ileocaecal junction, showed that mean T 50% ascending colon transit time of the 5 mm tablets was extended by codeine treatment (30 mg q.d.s.)…”