Popis: |
Numerous studies have shown that higher doses of nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with increased levels of mucosal injury and ulceration in both normal volunteers and patients. The present dose-ranging study was designed to determine whether escalating doses of a commonly prescribed NSAID, flurbiprofen, when expressed as mg/kg dosages, were associated with increased mucosal injury and ulceration. Subjects received either the recommended dose of 300 mg/day of flurbiprofen (N = 10), or the higher than recommended doses of 400 mg/day (N = 20) and 500 mg/day (N = 10), for a period of 7 days. Endoscopic examination was performed on day 0 and day 7, and the stomach was evaluated on day 7 for mucosal injury on a 0-4 scale, and for the presence or absence of ulcer. One gastric ulcer was seen in each of the 300- and 400-mg groups. However, in the 500 mg/day group, four gastric ulcers were seen (40%) (p = 0.04). Three of the six subjects developing gastric ulcer were of a fairly low body weight (two women, one man), and when the data were analyzed on a mg/kg basis, all six ulcers occurred in 19 of the 40 subjects receiving5.95 mg/kg, whereas no gastric ulcers were seen in the 21 subjects receiving dosages below that level (p0.01). These data suggest that, at least for this agent, a threshold level may exist above which gastric ulcers are much more likely to occur. This may in part explain why elderly debilitated, low-body-weight female patients are more prone to NSAID-related gastric ulcer. |