Comparison of the systemic inhibition of thromboxane synthesis, anti-inflammatory activity and gastro-intestinal toxicity of non-steroidal anti-inflammatory drugs in the rat

Carr, D. P.; Henn, Raphael; Green, J. R.; Böttcher, I.

doi:10.1007/bf01971260

Cited by 30 publications

(12 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding exhibited a possible dissociation between GI toxicity and TXB 2 inhibition. In addition, an animal study [41] demonstrated that within 24 h of NSAID (indomethacin, aspirin, or naproxen) administration TXB 2 inhibition had decreased to less than 50%, reflecting the short half-life of these drugs and the reversible nature of the cyclo-oxygenase inhibition.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Endoscopic Comparison of the Gastroduodenal Safety and the Effects on Arachidonic Acid Products between Meloxicam and Piroxicam in the Treatment of Osteoarthritis

et al. 2001

View full text Add to dashboard Cite

Our objective was to evaluate the efficacy, the gastroduodenal safety, and the effects on arachidonic acid products of meloxicam, a new acidic enolic non-steroidal anti-inflammatory drug which preferentially inhibits cyclo-oxygenase-2 over cyclo-oxygenase-1, versus piroxicam in patients with osteoarthritis of the knee. Meloxicam 7.5 mg or piroxicam 20 mg daily was administered for 4 weeks in this double-blind parallel-groups randomised study. The efficacy for pain relief of the two tested medications was assessed by means of visual analogue scale and other clinical parameters. Pre- and post-treatment endoscopies were performed, and the findings were scored and recorded. The gastric fluid was aspirated at each time and prostaglandin E2, thromboxane B2 and leukotriene B4 were determined by ELISA. There was no significant difference between the groups regarding the primary efficacy. Changes in endoscopic findings by means of Lanza score showed statistically significant differences between the two treatment groups in favour of meloxicam at all sites--gastric, duodenal and total. Within-group comparisons showed a statistically significant difference (worsening) in gastric and total score with piroxicam, but no significant difference with meloxicam. The frequency of clinically relevant cases (total score >2) also showed a statistically significant worsening in the piroxicam group. The better GI tolerability of meloxicam was also suggested by fewer adverse GI events and no withdrawals due to adverse events compared with piroxicam. The pre-/post-study gastric juice concentration of PGE2, TXB2, and LTB4 in the meloxicam group was 135.2 +/- 85.8/71.2 +/- 32.2, 116.3 +/- 81.7/99.4 +/- 107.5 and 388 +/- 321/223 +/- 98 pg/ml respectively. The pre-/post-study gastric juice concentration of PGE2, TXB2 and LTB4 in the piroxicam group was 105.7 +/- 43.1/68.2 +/- 34.9, 94.0 +/- 50.9/105.9 +/- 121.1 and 625 +/- 1574/828 +/- 1464 pg/ml, respectively. Both meloxicam and piroxicam significantly inhibited gastric PGE2 levels after 4 weeks' treatment; however, there was no difference between these two groups. Neither of these medications had an effect on TXB2. Only meloxicam inhibited LTB4 concentration significantly, and the between-groups difference was significant. Meloxicam 7.5 mg once daily had better gastrointestinal tolerability and an efficacy comparable to that of piroxicam 20 mg over 4 weeks in patients with osteoarthritis of the knee.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Because TXB 2 inhibition was NSAID dose dependent [41], we speculate that this unexpected observation may be caused by the low plasma level of these two medicines (piroxicam and meloxicam) and the long period of nil by mouth before gastroscopic examination and the last dose of medicine.…”

Section: Discussionmentioning

confidence: 99%

Endoscopic Comparison of the Gastroduodenal Safety and the Effects on Arachidonic Acid Products between Meloxicam and Piroxicam in the Treatment of Osteoarthritis

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Early experimental studies in rats demonstrated that at anti-inflammatory doses that reduced carrageenaninduced paw edema, nimesulide had no effect on gastric PG levels and did not cause bleeding of the gastric mucosa (Carr et al, 1986;Nakatsugi et al, 1996). Its selective inhibition of COX-2 has been demonstrated in vitro using purified enzymes; the IC 50 for COX-1 was 5-fold greater than that for COX-2 (Barnett et al, 1994;Cullen et al, 1998).…”

Section: A Treatment Of Inflammatory Diseasesmentioning

confidence: 99%

Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition

2004

View full text Add to dashboard Cite

“…The index for nimesulide, 4.6, was especially low when compared with 9 for ibuprofen, 10.1 for meclofenamic acid, 11.6 for phenylbutazone, 16.8 for flufenamic acid, 18.6 for naproxen, 24.7 for niflumic acid, 36 for flurbiprofen, 42.1 for ketoprofen and 77 for tolmetin. Moreover, compared with aspirin, indomethacin and naproxen, Carr et al [41] have demonstrated that nimesulide has anti-inflammatory activity in rat adjuvant arthritis at a dosage (0.2 mg.kg ¹1 ) far 438 lower than that associated with gastrointestinal blood loss (100 mg.kg ¹1 ).…”

Section: Animal Pharmacological Data Obtained With Nimesulidementioning

confidence: 99%

In vitro and in vivo pharmacological evidence of selective cyclooxygenase-2 inhibition by nimesulide: An overview

1997

Inflammation Research

136

View full text Add to dashboard Cite

Most available nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both the constitutive cyclooxygenase-1 (COX-1) and the inducible cyclooxygenase-2 (COX-2), resulting in inhibition of prostaglandin (PG) and thromboxane (TX) biosynthesis. The inhibition of COX-2 might be the cause of the favourable anti-inflammatory, analgesic and antipyretic effects of NSAIDs, whereas that of COX-1 might result in unwanted gastrointestinal, renal and possibly other side-effects. Nimesulide is a sulfonanilide compound with anti-inflammatory properties. Its pharmacological profile (better inhibition of PG synthesis in inflammatory areas than in gastric mucosa), suggested that it might be a selective inhibitor of COX-2. In several in vitro assays using either purified COX-2 and COX-1 preparations or cell preparations (both from animal and human origins) expressing COX-1 or COX-2, ten out of eleven different groups have demonstrated that nimesulide selectively inhibits COX-2. The COX-2/ COX-1 inhibitory ratio varies, according to the assay preparation, from about 0.76 to 0.0004 i.e. a 1.3 to 2,512-fold higher selectivity for COX-2 than for COX-1. Moreover, an in vivo whole blood assay performed on healthy volunteers demonstrated a significant fall in COX-2 PGE2 production without any effect on COX-1 TXB2 production in subjects treated with nimesulide (100 mg b.i.d. for 2 weeks) versus no effect on COX-2 PGE2 and an almost total suppression of COX-1 TXB2 in subjects treated with aspirin (300 mg t.i.d. for 2 weeks). Nimesulide can thus be considered a relatively selective COX-2 inhibitor. At the recommended dosage of 100 mg b.i.d., it is as effective an analgesic and anti-inflammatory agent as classical NSAIDs, and a well-tolerated drug with few side-effects according to large-scale open studies and a global evaluation of a large number of controlled and non-controlled comparative trials.

show abstract

Comparison of the systemic inhibition of thromboxane synthesis, anti-inflammatory activity and gastro-intestinal toxicity of non-steroidal anti-inflammatory drugs in the rat

Cited by 30 publications

References 1 publication

Endoscopic Comparison of the Gastroduodenal Safety and the Effects on Arachidonic Acid Products between Meloxicam and Piroxicam in the Treatment of Osteoarthritis

Endoscopic Comparison of the Gastroduodenal Safety and the Effects on Arachidonic Acid Products between Meloxicam and Piroxicam in the Treatment of Osteoarthritis

Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition

In vitro and in vivo pharmacological evidence of selective cyclooxygenase-2 inhibition by nimesulide: An overview

Contact Info

Product

Resources

About