Optimal Assessment of Gastrointestinal Side Effects Induced by Non-Steroidal Anti-Inflammatory Drugs: Endoscopic Lesions, Faecal Blood Loss, and Symptoms Not Necessarily Correlated, As Observed after Naproxen and Oxindanac in Healthy Volunteers

Abstract

Gastrointestinal side effects caused by naproxen and oxindanac (a developmental non-steroidal anti-inflammatory drug) were compared by combined endoscopy and determination of faecal blood loss in 16 healthy male volunteers in a randomized, double-blind, crossover study. Individual daily faecal blood loss was determined by means of ^5lCr-labelled erythrocytes. Gastroduodenoscopy was performed before and after administration of naproxen, 750mg/day, and oxindanac, 600mg/day, for 1 week each. A washout period of at least 3 weeks was inserted between drug periods. Visual analogue scales (VAS) were used for endoscopic assessment of lesions and subjective complaints. Mean faecal blood loss increased from a base line 0.48 ml/ 24 h to 1.59 ml/24 h with naproxen (p<0.01) and from 0.56 ml/24 h to 1.31ml/ 24 h with oxindanac (p < 0.01). VAS scores for gastroduodenal lesions increased significantly with both drugs. Naproxen caused a significantly greater increase than oxindanac (p < 0.05). There was no correlation between gastrointestinal blood loss and endoscopic findings. Subjective symptoms were correlated to faecal blood loss with naproxen, but not to endoscopic findings. No such correlations were observed for oxindanac. Naproxen caused a significant prolongation of bleeding time (p < 0.01), whereas the increase caused by oxindanac was not significant (p = 0.09).

Key Words:

• Anti-inflammatory drugs
• endoscopy
• faecal blood loss
• naproxen
• nonsteroidal anti-inflammatory drugs
• oxindanac