Disease relevance of indomethacin

• Piperacillin and mezlocillin demonstrate significant activity against the Enterobacteriaceae, including many strains of Klebsiella pneumoniae against which the older penicillins carbenicillin, ticarcillin, and ampicillin are ineffective [1].
• Mezlocillin-induced thrombocytopenia [2].
• Acute interstitial nephritis associated with mezlocillin, nafcillin, and gentamicin treatment for Pseudomonas infection [3].
• Aztreonam was found to be more active than third-generation cephalosporins and comparable with mezlocillin against Enterobacter spp., Morganella, and Citrobacter freundii [4].
• Hypoprothrombinemia in patients with cancer receiving cefoperazone and mezlocillin [5].

High impact information on indomethacin

• The fall in single nephron GFR (SNGFR, nl.min-1) with increasing LH perfusion was unchanged after vehicle (10.9 +/- 2.8-11.2 +/- 0.8) but was blunted (P less than 0.05) by 45-55% in rats given indo (13.9 +/- 1.2-6.2 +/- 2.2) or UK (12.8 +/- 2.1-7.0 +/- 1.5) [6].
• Indo and perhaps other NSAIDs that enter the bile may damage the mucosa, not by a direct action, but by competing for the available protective PC molecules [7].
• Neither the rise in IL-6 nor the activation of signal transducer and activator of transcription-3 (STAT3) that is seen during liver regeneration is inhibited by indocin or the selective COX antagonists [8].
• In contrast, indocin treatment prevents the activation of CREB by phosphorylation that occurs during hepatic regeneration [8].
• In accordance with our hybridization results, an increase in IL-1 activity was obtained when eosinophils were stimulated with LPS and treated with indomethacine [9].

Chemical compound and disease context of indomethacin

• In the presence of ESRD, coadministration of mezlocillin increased the t1/2 of cefotaxime to 5.8 hours [10].
• It was especially active against Pseudomonas aeruginosa and as active as mezlocillin and piperacillin against Klebsiella pneumoniae [11].
• The impacts of meningeal infection with Pseudomonas aeruginosa and route of drug administration on the penetration of azlocillin and mezlocillin into the cerebrospinal fluid of rabbits were evaluated [12].
• Forty-three patients acquired nosocomial infections with ampicillin-resistant enterococci, most of which were also resistant to mezlocillin, piperacillin, and imipenem [13].
• These studies document that mezlocillin and ticarcillin were both effective in reducing the numbers of E. aerogenes CFU in vegetations in rabbits with experimental endocarditis when the drugs were given over a prolonged course [14].

Biological context of indomethacin

• Mezlocillin pharmacokinetics in renal impairment [15].
• The apparent Km is so low that after therapeutic doses of mezlocillin the kinetics are nonlinear for several hours [16].
• The data revealed that mezlocillin and piperacillin have significantly different pharmacokinetic reactions in the postpartum patient at the doses used [17].
• Eighteen subjects were randomized to receive mezlocillin, 4 g every 6 h; carbenicillin, 7.5 g every 6 h; or placebo, 50 ml every 6 h, each given for 20 intravenous doses unless the template bleeding time after 10 doses was greater than 15 min [18].
• The activities of the platelet aggregation test in vitro were significant but lower than those of the reference substances (indomethacine and acetylsalicylic acid) [19].

Anatomical context of indomethacin

• The half-life of mezlocillin in cerebrospinal fluid (CSF) was approximately twice that in serum of experimentally infected animals, and the penetration of drug into CSF was 5 to 15% after a single dose and 5 to 20% after continuous-infusion experiments [20].
• Assays performed during surgery after intravenous administration of 2 g of mezlocillin (n = 10) showed antibiotic activity of 895 +/- 196 micrograms/ml in the common duct bile and 402 +/- 133 micrograms/ml in the gallbladder bile [21].
• Multi-institutional study of mezlocillin therapy of urinary tract infections [22].
• Serum and sputum mezlocillin concentrations were measured microbiologically on the first treatment day [23].
• Penetration of mezlocillin into pancreatic juice [24].

Associations of indomethacin with other chemical compounds

• Concomitant administration of cefotaxime did not alter the pharmacokinetics of mezlocillin [10].
• The kinetics of intravenous mezlocillin was studied in 8 patients with creatinine clearances under 7 ml/min who were undergoing chronic hemodialysis [25].
• To determine whether prostaglandins (PGs) mediate the ACTH response to tumor necrosis factor-alpha (TNF alpha), indomethacin (Indo; 0.1-1.0 mg/kg, iv) was administered before TNF alpha (1 microgram, iv) in freely moving, alert rats [26].
• Comparative study of anti-pseudomonas activity of azlocillin, mezlocillin, and ticarcillin [27].
• Sulbactam and clavulanic acid: studies of enzyme kinetics and synergy with ampicillin and mezlocillin [28].

Gene context of indomethacin

• Carboxyfluorescein served as a substrate for MRP-mediated drug efflux, and indomethacine was the positive control used as an inhibitor of MRP in the flow cytometric experiments [29].
• The administration of IND also increased the myeloperoxidase (MPx) activity, which shows neutrophil infiltration into the gastric mucosal tissues [30].
• IND caused oxidative stress, which resulted in LPO in tissues, by decreasing the levels of GPx, SOD and GSH as compared to healthy rats [30].
• Indomethacin (INDO) does not effect expression of HUVEC class I or class II MHC molecules induced by TNF, IFN-gamma, or the combination of these mediators [31].
• We studied the effects of exogenous T cell growth factor (TCGF) (= interleukin-2) and indomethacine on the lymphocyte transformation response in vitro to allogeneic cells, mitogens, and antigens in AIDS patients, those with AIDS-related complex (ARC), and in healthy controls [32].

Analytical, diagnostic and therapeutic context of indomethacin

• A seminal level of 42 micrograms/mL of mezlocillin was documented by bioassay [33].
• A dosage schedule for use of intravenous mezlocillin in patients undergoing hemodialysis is presented [25].
• To establish elimination kinetics of mezlocillin in patients with hepatic insufficiency, we gave eight normal subjects and four patients with hepatic insufficiency and normal renal function a single 3-gm dose of mezlocillin by intravenous infusion [34].
• Solid-phase ion-pair extraction and liquid chromatography of mezlocillin in serum [35].
• In 10 cholecystectomized patients provided with a T-tube, intramuscular injection of 1 g of mezlocillin resulted in a biliary peak concentration of 295.7 +/- 58.1 micrograms/ml [21].

References