Disease relevance of ZOMEPIRAC SODIUM

• Apparent anaphylactic reaction to zomepirac (Zomax) [1].
• These results indicate that zomepirac gave excellent relief of the symptoms of dysmenorrhea in this study population [2].
• Orally administered zomepirac and parenterally administered morphine. Comparison for the treatment of postoperative pain [3].
• Nonoliguric renal failure associated with zomepirac [4].
• Anaphylactic shock, acute renal failure, and disseminated intravascular coagulation. Suspected complications of zomepirac [5].

Psychiatry related information on ZOMEPIRAC SODIUM

• Evaluation for withdrawal symptoms following chronic zomepirac administration [6].
• Zomepirac: preclinical narcotic abuse liability evaluation [7].

High impact information on ZOMEPIRAC SODIUM

• We believe that these cases represent type 3 allergic reactions to zomepirac [8].
• Zomepirac-induced serum sickness. A report of two cases [8].
• Stomatitis associated with zomepirac [9].
• Given orally, zomepirac has provided analgesia comparable with usual intramuscular doses of morphine in postoperative pain [10].
• Formation of irreversibly protein-bound zomepirac occurs via the acyl glucuronide as previously shown for bilirubin glucuronide, and the reaction may be general for other drugs that are metabolized to acyl glucuronides [11].

Chemical compound and disease context of ZOMEPIRAC SODIUM

• In patients with liver disease, the reduction in zomepirac clearance was significantly correlated with the abnormalities in galactose elimination capacity (r = 0.83, n = 18), suggesting that the functioning liver cell mass was the major determinant of the rate of zomepirac disposition [12].
• Although zomepirac (ZP) and tolmetin (TM) induce anaphylactic reactions and form reactive acyl glucuronides, a direct link between the two events remains obscure [13].
• A case of acute renal failure in a chronic acetaminophen abuser receiving concurrent zomepirac therapy is reported [14].

Biological context of ZOMEPIRAC SODIUM

• The nature of the zomepirac protein binding is probably covalent [11].
• Irreversible binding of zomepirac to protein was determined by exhaustive washing of protein, followed by hydrolysis of bound zomepirac-protein adduct with base, extraction of the liberated drug, and chromatographic measurement [11].
• Kinetics of zomepirac, an oral, nonnarcotic analgesic, were studied in healthy males in 3 clinical experiments [15].
• Bioavailability of zomepirac from the 3 dosage forms was much the same [15].
• Probenecid decreased the renal clearance of zomepirac glucuronide by 72%, which, together with the increased zomepirac levels, resulted in a 2.8-fold increase in the AUC of the conjugate [16].

Anatomical context of ZOMEPIRAC SODIUM

• The patient's lymphocytes showed no proliferative response to zomepirac [17].
• The effect of zomepirac on red blood cell survival and immune system [18].
• In a separate series of experiments, zomepirac (10 mg/kg i.v.), given 30 min before occlusion, failed to limit the extent of irreversible myocardial injury after temporary (90 min) LCX coronary artery occlusion in the canine [19].
• Bile duct ligation promotes covalent drug-protein adduct formation in plasma but not in liver of rats given zomepirac [20].
• In HT-29 cells incubated with zomepirac, covalently modified proteins in cytosol were detected by immunoblotting with a zomepirac antibody, suggesting that HT-29 cells do have the capacity to glucuronidate zomepirac [21].

Associations of ZOMEPIRAC SODIUM with other chemical compounds

• In vitro drug binding was also observed for the isomers of zomepirac glucuronide which were formed by intramolecular acyl migration [11].
• Probenecid decreased total plasma clearance of zomepirac by 64%, which resulted in an increase in bioavailability from 0.55 without probenecid to 0.84 when given concurrently [16].
• In contrast, zomepirac did not inhibit [cAMP]i generation or stimulate cell migration but weakly antagonized the effects of indomethacin on [cAMP]i. Together, these results reveal structural features of arylacetic acid NSAIDs that may be exploited for the development of selective CRTH2 ligands [22].
• Human serum albumins modified by covalently bound tolmetin or zomepirac were synthesized as models for similar products formed in vivo from acyl glucuronides [23].
• When acyl glucuronide metabolites of two previously marketed acidic drugs, zomepirac and suprofen, were incubated with albumin at a concentration of 2.5 mM, more fluorescent product was formed than by 500 mM glucose [24].

Gene context of ZOMEPIRAC SODIUM

• Clinical comparison of zomepirac with APC/codeine combination in the treatment of pain following oral surgery [25].
• Bovine brain microtubular protein (MTP) was purified by assembly-disassembly cycles and incubated with the nonsteroidal anti-inflammatory drug (NSAID) zomepirac (ZP), its acyl glucuronide (ZAG) and rearrangement isomers (iso-ZAG) at various concentrations for 2 h at room temperature and pH 7 [26].
• Nonsteroidal anti-inflammatory agents, Part IV - A new analgesic: zomepirac [27].
• Zomepirac failed to displace tritiated etorphine significantly at concentrations up to 200 mumol/l. It was active (3-7 X 10(-5) mol/l) on both the electrically stimulated guinea pig ileum and mouse vas deferens but was less efficacious than morphine; these effects were not reversed by narcotic antagonists [7].

Analytical, diagnostic and therapeutic context of ZOMEPIRAC SODIUM

• Following oral administration of zomepirac (200 mg), plasma and urinary drug concentrations were measured by high-pressure liquid chromatography [12].
• Hemodialysis increased zomepirac binding to plasma of uremic patients, but NEFA concentrations were also increased in hemodialyzed plasma [28].
• Morphine (15 and 30 mg), but not zomepirac (400 and 800 mg), induced pupillary constriction and characteristic morphinelike subjective effects [29].
• Diflunisal (MK-647; 5-(2,4-difluorophenyl)salicylic acid] exhibited activity in this assay after oral administration with potency about 25 times greater than that of aspirin, about 3 times that of glafenine and twice that of zomepirac [30].
• Since zomepirac is highly bound to plasma proteins (approximately 98%), only a small fraction of the drug is available for filtration at the glomerulus [31].

References