Disease relevance of Dynastat

• The contribution of KRAS-dependent COX-2 to early metastatic tumor cell seeding (by intravital microscopy) and outgrowth of metastases in the liver (by bioluminescence imaging) was studied by using parecoxib, a novel and highly selective liver-activated COX-2 inhibitor [1].
• Parecoxib tolerability in patients with hypersensitivity to nonsteroidal anti-inflammatory drugs [2].
• While pain ratings were not affected, parecoxib as well as paracetamol significantly reduced the areas of secondary hyperalgesia to pinprick and touch [3].
• Selective cyclo-oxygenase-2 inhibition with parecoxib acutely impairs endothelium-dependent vasodilatation in patients with essential hypertension [4].
• The most common adverse events irrespective of treatment (parecoxib, ketorolac or placebo) after dental surgery were nausea, alveolar osteitis, dizziness and headache [5].

Psychiatry related information on Dynastat

• In eight healthy subjects, a freeze lesion was induced and mechanical pain thresholds (MPT) were tested for 5h following administration of the non-selective COX inhibitor diclofenac (75mg), the COX-2-selective inhibitor parecoxib (40mg) or placebo in a randomized, double-blind cross-over study [6].

High impact information on Dynastat

• To examine the role of prostaglandin in this response, we investigated whether 24-h BUO changed the expression of cyclooxygenases (COX-1 and -2) in the kidney and tested the effect of the selective COX-2 inhibitor parecoxib (5 mg.kg(-1).day(-1) via osmotic minipumps) on AQPs and sodium transport [7].
• Immunohistochemistry for AQP2, NHE3, and BSC-1 confirmed the effect of parecoxib [7].
• Parecoxib had no significant effect on the Na-K-ATPase alpha(1)-subunit, type II Na-P(i) cotransporter, or AQP3 [7].
• The cyclooxygenase isozyme inhibitors parecoxib and paracetamol reduce central hyperalgesia in humans [3].
• In clinical trials, valdecoxib, parecoxib, etoricoxib and lumaricoxib have caused no more endoscopic ulcers than placebo [8].

Chemical compound and disease context of Dynastat

• CONCLUSION: COX-2 inhibition with the prodrug, parecoxib, diminishes the acetylcholine-induced vasodilatation in the forearm circulation of patients with essential hypertension [4].
• CONCLUSIONS: Parecoxib and valdecoxib are useful adjuncts to opioids for the treatment of postoperative pain in noncardiac surgical patients [9].
• Postsurgical intravenous administration of the cyclooxygenase 1/2 inhibitor ketorolac, and especially the cyclooxygenase 2 inhibitor parecoxib, reduces cerebrospinal fluid prostaglandin E2 concentration and postoperative pain [10].
• In this prospective, randomized, double-blind, double-dummy study, we randomly assigned 182 patients scheduled for initial inguinal hernia repair under general anesthesia to receive a single injection of 40 mg parecoxib or 2 injections of 2 g propacetamol within the first 12 h after surgery [11].
• In the pregabalin + parecoxib treated group, the area of allodynia was significantly reduced (P < 0.0001) and the area of hyperalgesia insignificantly attenuated (P = 0.09) vs placebo + parecoxib; no efficacy improvement was observed with aprepitant + parecoxib [12].

Biological context of Dynastat

• This investigation determined the influence of parecoxib on the pharmacokinetics and pharmacodynamics of bolus dose propofol in human volunteers [13].
• CONCLUSION: Intravenous parecoxib (20 or 40 mg) was effective in decreasing the PCA opioid requirement after lower abdominal surgical procedures [14].
• Influence on platelet aggregation of i.v. parecoxib and acetaminophen in healthy volunteers [15].
• Coadministration of parecoxib 40 mg bid IV with UFH (treatment period II) had no significant effect on aPTT, PT, or platelet counts, which were similar to those of participants receiving UFH alone (treatment period I) at all time points [16].
• Finally, the efficacy of RIT alone [125 microCi 131I-MN-14/mouse approximately 1/4 of the maximal tolerated dose (MTD)] was compared with that of Parecoxib monotherapy and RIT combined with daily injections of Parecoxib (1.0 or 5.0 mg/kg) [17].

Anatomical context of Dynastat

• IV parecoxib (40 mg twice daily for 7 days) produced significantly fewer gastrointestinal erosions and/or ulcers than ketorolac (15 mg 4 times a day for 5 days) in healthy volunteers in a well controlled trial; effects on upper gastrointestinal mucosa were similar for parecoxib and placebo [5].
• BACKGROUND: Valdecoxib and its intravenous prodrug parecoxib are reported to increase thromboembolic risk after coronary artery bypass grafting [9].
• RESULTS: Parecoxib significantly attenuated PPE in the rat dura mater [18].
• Parecoxib impairs early tendon repair but improves later remodeling [19].
• However, parecoxib was without any effect on gastric mucosa [20].

Associations of Dynastat with other chemical compounds

• BACKGROUND: Parecoxib is a parenteral cyclooxygenase-2 (COX-2) inhibitor intended for perioperative analgesia [21].
• Venous concentrations of propofol, parecoxib, and parecoxib metabolites were determined by mass spectrometry [13].
• Neither GW9662 nor parecoxib affected the cardioprotective effects of ischemic preconditioning [22].
• Subjects received both alfentanil (15 microg/kg) and fentanyl (5 microg/kg; 15-min intravenous infusion) 1 h after placebo, parecoxib (40 mg intravenously every 12 h), or troleandomycin (every 6 h) [21].
• Animals were also subjected to either 1) ischemic preconditioning alone, ischemic preconditioning, and pretreated with either GW9662 or parecoxib (20 mg/kg) or 2) lipopolysaccharide (LPS) (1 mg/kg) alone, LPS, and pretreated with ciglitazone, GW9662, or parecoxib (20 mg/kg) [22].

Gene context of Dynastat

• These results demonstrate that ketorolac and parecoxib delay fracture healing in this model, but in this study daily administration of ketorolac, a non-selective COX inhibitor had a greater affect on this process [23].
• Recently, other selective COX-2 inhibitors with different COX-1/COX-2 selectivity and pharmacokinetic features have been developed, i.e. valdecoxib, parecoxib, etoricoxib and lumiracoxib [24].
• The antinociceptive, anti-inflammatory, antipyretic effects along with gastric safety profile of parecoxib, a novel, potent selective cyclooxygenase-2 inhibiting prodrug, and those of ketorolac, a nonselective cyclooxygenase inhibitor, were evaluated in various animal models [20].
• We also investigated the effects of the selective cyclooxygenase-2 inhibitor, parecoxib, on ischemic preconditioning and delayed cardioprotective effects of endotoxin [22].
• Parecoxib did not affect CYP3A4 activity as assessed using midazolam clearance as the in vivo probe [25].

Analytical, diagnostic and therapeutic context of Dynastat

• Patients were allocated randomly to groups to receive the non-selective COX-inhibitor, acetylsalicylate-lysin (500 mg intravenously), or the selective COX-2 inhibitor, parecoxib, an injectable prodrug of valdecoxib (20 mg intravenously) [4].
• BACKGROUND: The analgesic efficacy and side effect profile of intravenous parecoxib, a novel cyclooxygenase type-2 (COX-2) inhibitor, was assessed in a double-blinded, placebo-controlled study involving patients undergoing major gynecologic surgical procedures [14].
• In this multicenter, double-blinded, randomized, placebo-controlled study we evaluated the analgesic and opioid-sparing efficacy of a preoperative dose of i.v. parecoxib followed by oral valdecoxib in treating pain associated with elective laparoscopic cholecystectomy [26].
• Patients were allocated at a ratio of 2:1 to parecoxib/valdecoxib or standard care (control) groups, respectively [27].
• OBJECTIVE: We aimed to investigate the effects of the cyclooxygenases-2 (COX-2) inhibitor parecoxib on meningeal plasma protein extravasation (PPE) and on c-fos expression in the nucleus trigeminalis caudalis in an animal model of trigeminovascular activation [18].

References