The pro-drug sulindac may reduce the risk of intestinal damage associated with the use of conventional non-steroidal anti-inflammatory drugs.
To test the hypothesis that administration of a non-steroidal anti-inflammatory drug formulated as a pro-drug, inactive as a cyclooxygenase inhibitor until after absorption, might cause less intestinal damage than conventional non-steroidal anti-inflammatory drugs, intestinal permeation to 51Cr-EDTA and mannitol was assessed in healthy volunteers before and after oral treatment for 1 week with either the pro-drug sulindac or the conventional non-steroidal anti-inflammatory drug indomethacin. Indomethacin, but not sulindac, significantly increased intestinal permeation to 51Cr-EDTA and reduced haemoglobin and haematocrit; neither affect mannitol permeation.
Davies
G R
GR
Gastrointestinal Science Research Unit, London Hospital Medical College, UK.
Rampton
D S
DS
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004492:Edetic Acid / Q000493:pharmacokinetics; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects / Q000494:pharmacology; D007410:Intestinal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008353:Mannitol / Q000493:pharmacokinetics; D008875:Middle Aged; D010539:Permeability / Q000187:drug effects; D011355:Prodrugs / Q000009:adverse effects*; D013467:Sulindac / Q000009:adverse effects / Q000627:therapeutic use*; D014508:Urea / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011355:Prodrugs; D013467:Sulindac; D008353:Mannitol; D014508:Urea; D004492:Edetic Acid; D007213:Indomethacin