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Interleukin-1beta and ibuprofen effects on CD4/CD8 cells after endotoxic challenge.

Mansilla-Rosello A, Ferron-Orihuela JA, Ruiz-Cabello F, Garrote-Lara D, Delgado-Carrasco S, Tamayo-Pozo F.

Experimental Surgery Unit, Virgen de las Nieves Foundation, Granada, Spain.

Multiple-organ failure is considered a consequence of autodestructive inflammatory response during which a state of immunosuppression is produced. Alterations in CD4 and CD8 lymphocytes after experimental endotoxic challenge and their correlation with the protective effects of interleukin-1beta (IL-1beta) and ibuprofen pretreatment were investigated. CBA/H mice were injected with lipopolysaccharide (LPS) of Escherichia coli (125 mg/kg); 40 mice were pretreated with IL-1beta (80 ng/mouse, 24 hr pre-LPS), 40 with ibuprofen (1 mg/kg 1 hr pre-LPS, 1 mg/kg 30 min post-LPS), and 40 with both drugs (same doses and timing). Prostaglandin E2 (PGE2) urine levels were determined 4, 8, and 12 hr post-LPS (10 mice), CD4 and CD8 cells 24 hr post-LPS (10 mice), and mortality at 24, 48, 72, and 96 hr (20 mice). PGE2 decreased in ibuprofen-treated groups (P < 0.05 versus control, IL-1beta groups). CD4/CD8 ratio increased in groups treated with IL-1beta (11,9) and IL-1beta plus ibuprofen (11,2) compared with sham (3,4), LPS (4,2), and ibuprofen alone (4,1) (P < 0.05). Mortality decreased in all treated groups. A correlation was observed between IL-1beta treatment, CD4/CD8 ratio, and reduced mortality. In this model IL-1beta treatment improved survival after endotoxin challenge, preventing lymphocyte derangements and increasing CD4/CD8 ratio. This effect was not potentiated by ibuprofen administration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8895611&dopt=Abstract ibuprofen Motrin



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Use of a rapid HPLC assay for determination of pharmacokinetic parameters of ibuprofen in patients with cystic fibrosis.

Rifai N, Sakamoto M, Law T, Galpchian V, Harris N, Colin AA.

Department of Laboratory Medicine, Children's Hospital, Boston, MA 02115, USA. rifai al.tch.harvard.edu

High doses of ibuprofen have been shown to delay the progression of lung disease without serious adverse effects in patients with cystic fibrosis. To be effective, peak ibuprofen concentration of 50 to 100 mg/L has to be achieved. We developed an HPLC assay to rapidly determine plasma ibuprofen concentration. We used this assay to determine the pharmacokinetics of ibuprofen in patients with cystic fibrosis. The assay possessed linearity up to 500 mg/L, sensitivity to 1 mg/L, average recovery of 98%, and run-to-run precision (n = 23) of 3%. Furthermore, the assay proved to be free of interference from 51 medications. Observed time to peak concentration varied significantly between those receiving ibuprofen tablets (mean + SD, 94 +/- 29 min, n = 16) and syrup (30 +/- 0 min, n = 4) (P < 0.0001). We conclude that the method described here is ideal for therapeutic monitoring of ibuprofen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8906081&dopt=Abstract ibuprofen Motrin



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Treatment of an acute bacterial infection with a combination of acetylsalicylic acid/ibuprofen and interferon gamma.

Hockertz S, Heckenberger R.

Fraunhofer Department of Toxicology and Environmental Medicine, Hamburg.

The bacterial infection with Listeria monocytogenes is associated with an inhibition of the macrophage function, the first-line defense against bacterial infection. We studied the effect of acetylsalicylic acid (ASA, CAS 50-78-2) and ibuprofen (CAS 15687-21-1) alone and in combination with a suboptimal dose of recombinant interferon gamma. (IFN gamma) on the acute infection with Listeria monocytogenes in the Balb/c mouse. Animals were intravenously infected with a sublethal dose of Listeria monocytogenes. The therapy was carried out I) at the time of the infection, II) 30 min, III) 60 min, IV) 3 h and V) 24 h post infection. Six groups of mice were treated: i) untreated control, ii) 10(4) units IFN gamma, iii) 10 mg/kg ASA, i.v.) 10 mg/kg ASA + IFN gamma, i.v.) 12 mg/kg ibuprofen, and vi) 12 mg/kg ibuprofen + IFN gamma. The data shown that treatment with ibuprofen and ASA resulted in a significant reduction of viable bacteria in spleen and liver, the main organs of this infection. In combination with low dose interferon gamma, both non-steroidal anti-inflammatory drugs (NSAID) reduced the parasite burden in the examined organs by a factor of more than 10. The therapeutic efficacy showed its maximum 1 h after challenge with Listeria monocytogenes. These results suggest that ibuprofen and ASA possess antibacterial activity. In addition, IFN gamma significantly increases the antibacterial activity of ASA and ibuprofen. Presumably, these effects are due to an influence on the host immune system.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8931897&dopt=Abstract ibuprofen Motrin



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In-vitro evaluation of sustained release ibuprofen microspheres.

Ghaly ES, Sepulveda S.

School of Pharmacy, University of Puerto Rico, San Juan.

Microspheres for oral use have been employed to target and to sustain the release of the drug. The objective of this study was to use the melt dispersion technique and aqueous vehicle to entrap ibuprofen into wax carrier (carnauba wax) with the aid of surfactant (Pluronic L-62). The effects of different levels of Pluronic L-62, stirring speed, and ibuprofen levels, as well as the in-vitro release rate of ibuprofen were evaluated. The in-vitro dissolution of ibuprofen in phosphate buffer pH 7.2 showed that microspheres prepared with low amount of drug (1.5 g) released 58.1% of ibuprofen after 6 hours, while microspheres prepared with high amount of drug (6.0 g) released only 38.9% of ibuprofen. Microsphere formulations prepared by using aqueous vehicle were spherical and of smooth surface. In general the melt dispersion technique was a successful method for preparing sustained release ibuprofen microspheres.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8936613&dopt=Abstract ibuprofen Motrin



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Polymeric drugs derived from ibuprofen with improved antiinflammatory profile.

Liso PA, Rebuelta M, San Roman J, Gallardo A, Villar AM.

Departamento de Farmacologia, Facultad de Farmacia, Universidad Complutense de Madrid, Spain.

A new methacrylic monomeric compound bearing Ibuprofen (MIA) and the respective polymethacrylic macromolecular derivative (polyMIA) were evaluated for antiinflammatory properties in order to study their pharmacological activity profile. The macromolecular drug is constituted of Ibuprofen residues linked covalently to a polymethacrylic support, as a side substituent of the repeating unit, by means of a spacer group (p-aminophenoxy) that, in addition, is the most representative metabolite of Paracetamol. The Ibuprofen is slowly released from the polymeric support by hydrolysis of the ester bond in a biological medium. Different antiinflammatory testing methods were used; and the results obtained indicate that the monomeric and polymeric forms display higher potency to inhibit acute inflammatory processes than the traditional Ibuprofen form, even doubling the power of Ibuprofen. In addition, they present higher activity against chronic experimental processes, as well as an excellent antinociceptive behavior to inhibit the pain associated with arthritic diseases. According to previous reports and results presented in this article, we can conclude that the new polymethacrylic structures show higher analgesic, antipiretic, and antiinflammatory activities due to the possible activity of the macromolecular drug as well as to the controlled Ibuprofen release from the macromolecular delivery system. After releasing of the side active residue, a derivate of poly(sodium methacrylate) is formed, which is cleared from the body easily by the normal pathway of kidney metabolism.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8953145&dopt=Abstract ibuprofen Motrin



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Anti-inflammatory, analgesic and ulcerogenic properties of S-(+)-ibuproxam, racemic ibuproxam-beta-cyclodextrin and S-(+)-ibuproxam-beta-cyclodextrin.

Bole-Vunduk B, Verhnjak K, Zmitek J.

LEK Pharmaceutical and Chemical Company d.d., Research and Development, Ljubljana, Slovenia.

The anti-inflammatory, analgesic and gastric mucosal damage-inducing activities of S-(+)-ibuproxam, and S-(+)-ibuproxam-beta-cyclodextrin, new propionic acid derivatives, and racemic ibuproxam-beta-cyclodextrin were investigated in three animal models and compared with those of racemic ibuproxam, racemic ibuprofen and its optical enantiomer S-(+)-ibuprofen. The anti-inflammatory activities of racemic ibuprofen, S-(+)-ibuprofen and racemic ibuproxam in carrageenan-induced paw oedema in rats were almost equipotent and slightly greater than those of S-(+)-ibuproxam and S-(+)-ibuproxam-beta-cyclodextrin, and significantly greater than that of racemic ibuproxam-beta-cyclodextrin. In abdominal constriction tests in mice, the analgesic effects of racemic ibuproxam, S-(+)-ibuproxam, racemic ibuproxam-beta-cyclodextrin and S-(+)-ibuproxam-beta-cyclodextrin were significantly less pronounced than those of racemic ibuprofen and S-(+)-ibuprofen. Ulcerogenic activity of S-(+)-ibuproxam-beta-cyclodextrin in rats was found to be significantly weaker than that of racemic ibuproxam-beta-cyclodextrin, racemic ibuproxam and S-(+)-ibuproxam and, most notably, weaker than those of racemic ibuprofen and S-(+)ibuprofen. These results indicate that S-(+)-ibuproxam-beta-cyclodextrin could be a novel potent anti-inflammatory and analgesic agent with a therapeutic index more favourable than that of the classical non-steroid anti-inflammatory drugs ibuprofen and ibuproxam.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8961164&dopt=Abstract ibuprofen Motrin



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Ibuprofen protects human endothelial cell prostaglandin H synthase from hydrogen peroxide.

Wessels DA, Hempel SL.

Department of Veterans Affairs Medical Center, University of Iowa, Iowa City 52242, USA.

Human endothelial cells exposed to H2O2 demonstrate decreased prostacyclin (PGI2) synthesis due to decreased prostaglandin H synthase (PGH synthase) activity. We tested the hypothesis that PGH synthase activity could be protected from H2O2 by a reversible nonsteroidal anti-inflammatory drug. Experiments demonstrate that ibuprofen if present during H2O2 exposure, protects endothelial cell PGH synthase against the decrease in prostaglandin formation caused by H2O2. Additional studies demonstrated that decreasing arachidonic acid release from cell phospholipids during H2O2 exposure did not protect PGI2 synthesis following H2O2 exposure. In other experiments, ibuprofen did not chelate Fe2+ in a conformation that inhibited the reactivity of Fe2+. In addition, ibuprofen did not scavenge HO. However, we demonstrate that ibuprofen significantly protects purified PGH synthase cyclooxygenase activity from the effects of H2O2. The results confirm the hypothesis. These findings suggest that ibuprofen displaces oxidant species from the cyclooxygenase site of PGH synthase, thereby preventing oxidation of the functional groups important for PGH synthase activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8997188&dopt=Abstract ibuprofen Motrin



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Does ibuprofen affect bilirubin-albumin binding in newborn infant serum?

Cooper-Peel C, Brodersen R, Robertson A.

Department of Pediatrics, East Carolina University School of Medicine, Greenville, NC 27858-4354, USA.

Intravenous ibuprofen is being studied in sick, premature infants for the prevention of intraventricular haemorrhage and closure of the ductus arteriosus. We tested the effect of ibuprofen on bilirubin-albumin binding in adult and newborn infant serum by measuring the free ibuprofen concentration in the presence of bilirubin (reverse displacement method). At clinically appropriate ibuprofen concentrations the free fraction of bilirubin is increased by a factor of 4. Ibuprofen may increase the risk of bilirubin encephalopathy when used in sick, premature infants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9000255&dopt=Abstract ibuprofen Motrin