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Outcome of upper gastro-intestinal bleeding and use of ibuprofen versus paracetamol.

Blot WJ, Fischer T, Nielsen GL, Friis S, Mumma M, Lipworth L, DuBois R, McLaughlin JK, Sorensen HT.

International Epidemiology Institute, Rockville, Maryland, USA.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to increase the risk of upper gastrointestinal bleeding (UGIB). Whether the severity of outcome of UGIB associated with NSAIDs differs from non-NSAID-related UGIB is less clear. METHOD: Medical records of 228 patients hospitalized for UGIB in the Danish county of North Jutland were evaluated. Preadmission characteristics and clinical outcomes were compared between 112 patients who had been prescribed ibuprofen and 116 patients who had been prescribed paracetamol within 90 days of the hospitalization. RESULTS: The baseline characteristics of UGIB patients prescribed ibuprofen tended to differ from those prescribed paracetamol. The ibuprofen group significantly less often had histories of ulcer (11% vs 36%) and dyspepsia (19% vs 44%), or had been prescribed medications for these or other conditions, and had lower co-morbidity indices. Ibuprofen users also were somewhat less likely (31% vs 37%) to report GI pain at admission, but among hospitalized patients with endoscopic examinations were more likely (75% vs 58%) to be diagnosed with ulcer or hematemesis vs normal or gastritis/dyspepsia/reflux. For the clinical outcomes, 30 days case fatality rates were 12% for both ibuprofen and paracetamol users. The ibuprofen-related cases of UGIB more often required surgery (11% vs 3%) or transfusions (66% vs 57%), and those prescribed ibuprofen averaged 11 days in hospital, 4 days longer than those prescribed paracetamol. Adjustment for baseline characteristics and underlying conditions, or analyses eliminating patients with unconfirmed diagnoses and prior ulcers or restricted to patients with current hospital diagnoses of ulcer or hematemesis, did not materially alter the ibuprofen vs paracetamol differences in outcome measures. Generally similar results were obtained when restricting the analyses to patients prescribed ibuprofen or paracetamol within 30 days of UGIB hospitalization, except for a reduction in the 30 days case fatality rate among those prescribed ibuprofen. CONCLUSIONS: UGIB patients with antecedent ibuprofen prescriptions experienced about the same case fatality rates, but more surgery and longer hospital stays, than patients prescribed paracetamol. The differences appear in part due to differing characteristics among those prescribed ibuprofen compared with those prescribed paracetamol, but also raise the possibility of drug-related effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15683100&dopt=Abstract ibuprofen Motrin



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Ibuprofen Suppresses Interleukin-1beta Induction of Pro-Amyloidogenic alpha(1)-Antichymotrypsin to Ameliorate beta-Amyloid (Abeta) Pathology in Alzheimer's Models.

Morihara T, Teter B, Yang F, Lim GP, Boudinot S, Boudinot FD, Frautschy SA, Cole GM.

[1] 1Greater Los Angeles VA Healthcare System, GRECC, Sepulveda, CA, USA [2] 3Department of Medicine, University of California, Los Angeles, CA, USA.

Epidemiological and basic research suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) should protect against the most common forms of Alzheimer's disease (AD). Ibuprofen reduces amyloid (Abeta) pathology in some transgenic models, but the precise mechanisms remain unclear. Although some reports show select NSAIDs inhibit amyloid production in vitro, the possibility that in vivo suppression of amyloid pathology occurs independent of Abeta production has not been ruled out. We show that ibuprofen reduced Abeta brain levels in rats from exogenously infused Abeta in the absence of altered Abeta production. To determine whether ibuprofen inhibits pro-amyloidogenic factors, APPsw (Tg2576) mice were treated with ibuprofen for 6 months, and expression levels of the Abeta and inflammation-related molecules alpha(1) antichymotrypsin (ACT), apoE, BACE1, and peroxisome proliferator-activated receptor gamma) (PPARgamma) were measured. Among these, ACT, a factor whose overexpression accelerates amyloid pathology, was reduced by ibuprofen both in vivo and in vitro. IL-1beta, which was reduced in our animals by ibuprofen, induced mouse ACT in vitro. While some NSAIDs may inhibit Abeta42 production, these observations suggest that ibuprofen reduction of Abeta pathology may not be mediated by altered Abeta42 production. We present evidence supporting the hypothesis that ibuprofen-dependent amyloid reduction is mediated by inhibition of an alternate pathway (IL-1beta and its downstream target ACT).Neuropsychopharmacology advance online publication, 26 January 2005; doi:10.1038/sj.npp.1300668.

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The effect of systemic administration of ibuprofen in the experimental gingivitis model.

Sekino S, Ramberg P, Lindhe J.

Department of Periodontology, Faculty of Odontology, The Sahlgrenska Academy at Goteborg University, Goteborg, Sweden.

Sekino S, Ramberg P, Lindhe, J: The effect of systemic administration of ibuprofen in the experimental gingivitis model. J Clin Periodontol 2005; 32: 193-199. doi: 10.1111/j.1600-051X.2005.00671.x. (c) Blackwell Munksgaard, 2005. Abstract Background: Studies in humans have indicated that systemically administered flurbiprofen and ibuprofen may reduce gingivitis. De novo plaque formation is enhanced at tooth surfaces adjacent to inflamed gingivae. Objective: The aim of the present clinical trial was to evaluate the effect of systemic administration of ibuprofen on gingivitis and plaque build-up. Material and Methods: Eleven subjects were recruited for the study and were given oral hygiene instruction, scaling and professional mechanical tooth cleaning (PTC). At the end of a preparatory period (Day 0), the participants were told to abstain from all mechanical plaque control measures during a 2-week experimental period but to rinse with an assigned mouth rinse (positive control: 0.1% chlorhexidine digluconate; negative control: saline) or administer ibuprofen (tablets of 200 mg twice daily). Mouth rinsing was performed twice a day (after breakfast and in the evening), for 60 s with 10 ml. Re-examination was performed after 14 days of experiment. After a 2-week "wash-out" period, the participants received a new PTC and a second 14-day experimental period was initiated. The experimental and "wash-out" periods were repeated until all volunteers had been involved in all three regimens. Dental plaque was scored using the Quigley & Hein Plaque Index system and gingivitis according to the Gingival Index (GI) system. Supragingival plaque was collected and prepared for dark-field microscopy. One hundred bacterial cells were counted and classified into six different groups: coccoid cells, straight rods, filaments, fusiforms, spirochetes and motile rods. Gingival crevicular fluid (GCF) was collected from the same sites that were sampled for plaque. The volume of GCF collected in each strip was measured and analysed regarding content of lactoferrin and albumin. Results: During the period when the panelists rinsed with saline they accumulated large amounts of plaque and developed marked signs of gingivitis. When they rinsed with chlorhexidine digluconate, small amounts of plaque formed and few sites received GI score>/=2. After the 2 weeks of ibuprofen administration, the panelists presented with significantly fewer sites that scored GI>/=2 but had formed similar amounts of plaque as during the negative control period. Conclusion: It is suggested that ibuprofen administered via the systemic route has an effect on gingivitis but not on de novo plaque formation.

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[Antipyretic effectiveness of ibuprofen and paracetamol.]

[Article in Spanish]

Carabano Aguado I, Jimenez Lopez I, Lopez-Ceron Pinilla M, Calvo Garcia I, Pello Lazaro A, Balugo Bengoechea P, Baro Fernandez M, Ruiz Contreras J.

Departamento de Pediatria. Hospital Materno-Infantil 12 de Octubre. Madrid. Espana.

Objective. To compare the antipyretic effectiveness of ibuprofen and paracetamol and to evaluate the possible influence of patients' sex, weight, height and underlying disease on effectiveness. Patients and methods. A total of 166 children with fever, defined as a temperature equal to or above 38 degrees C, were enrolled. Of these, 80 were given paracetamol at a dose of 15 mg per kg and 86 were given 7 mg of ibuprofen per kg. Temperature was recorded at 60, 120,180 and 240 minutes after drug administration. Data were statistically analyzed, including analysis of paired data. Results. Ninety percent of the children became afebrile at some time during the study with both paracetamol and ibuprofen. Seventy-four percent of the patients remained afebrile 4 hours after drug administration. The mean temperatures obtained with ibuprofen versus paracetamol were 37.66 6 0.73 vs 37.8 6 0.65, p 5 0.22 one hour after drug administration; 37.09 6 0.83 vs 37.29 6 0.71, p 5 0.14 two hours after drug administration; 37.12 6 1.05 vs 37.28 6 0.87, p 5 0.64 three hours after drug administration; and 37.40 6 1.12 vs 37.46 6 1.00, p 5 0.72 four hours after drug administration. The maximum rate of temperature decrease was achieved during the first 60 minutes after drug administration (-1.32 6 0.83 with ibuprofen vs -1.09 6 0.77 with paracetamol, p 5 0.10). In children aged between 5 and 12 years, ibuprofen achieved significantly lower temperatures than paracetamol (38.00 6 0.65 vs 37.45 6 0.43, p 5 0.02 at 1 hour; 36.71 6 0.66 vs 37.60 6 0.93, p 5 0.01 at 2 hours; 36.80 6 0.79 vs 37.67 6 1.12, p 5 0.03 at 3 hours). Analysis by weight, height or underlying disease revealed no significant differences. Conclusions. Both ibuprofen and paracetamol proved to be successful in reducing temperature. The effectiveness of ibuprofen and paracetamol was similar, except in children aged more than 5 years old, in whom ibuprofen was more effective. Weight, sex and underlying disease had no influence on effectiveness.

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Solid-phase microextraction and chiral HPLC analysis of ibuprofen in urine.

de Oliveira AR, Cesarino EJ, Bonato PS.

Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Av. do Cafe S/N, 14040-903 Ribeirao Preto, Sao Paulo, Brazil.

A simple and rapid solid-phase microextraction method was developed for the enantioselective analysis of ibuprofen in urine. The sampling was made with a polydimethylsiloxane-divinylbenzene coated fiber immersed in the liquid sample. After desorptioning from the fiber, ibuprofen enantiomers were analyzed by HPLC using a Chiralpak AD-RH column and UV detection. The mobile phase was made of methanol-pH 3.0 phosphoric acid solution (75:25, v/v), at a flow rate of 0.45mL/min. The mean recoveries of SPME were 19.8 and 19.1% for (-)-R-ibuprofen and (+)-(S)-ibuprofen, respectively. The method was linear at the range of 0.25-25mug/mL. Within-day and between-day assay precision and accuracy were below 15% for both ibuprofen enantiomers at concentrations of 0.75, 7.5 and 20mug/mL. The method was tested with urine quality control samples and human urine fractions after administration of 200mg rac-ibuprofen.

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Administration of L-arginine reduces the delay of the healing process caused by ibuprofen. Implication of COX and growth factors expression.

Sanchez-Fidalgo S, Martin-Lacave I, Illanes M, Bruseghini L, Esteras A, Motilva V.

Departament of Pharmacolgy, Faculty of Pharmacy, University of Seville, Spain.

The objective of the present study has been to advance knowledge of the gastric role played by the amino acid L-Arginine (L-Arg) in the evolution of a chronic gastric ulcer. In order to clarify it, L-Arg alone or together with Ibuprofen have been administrated in an experimental acetic acid chronic ulcer, analysing characteristic parameters of an active curative process, such as PGE2 production, COX expression, and also angiogenesis, proliferation/apoptosis and growth factors expression. Our results reveal that L-Arg is favourable in the healing process improving the curative course. Ibuprofen caused a delay in ulcer healing, more evident 14 days after ulcer induction; COX-2 expression was increased at the 7th day although no signal of protein could be detected after 14 days; PGE2 production was inhibited in intact and ulcerated areas at both times assayed. In contrast, treatment with L-Arg reduced the delay of the lesion, the increment in COX-2 expression induced by Ibuprofen, and was able to maintain PGE2 levels similar to the control group after 14 days. Additionally, the histological study showed that the healing effects of L-Arg might be associated with an increased angiogenesis and FGF-2 expression. These actions could be considered key factors in the healing response associated with L-Arg administration. However, the proliferation study assayed with the PCNA-immunostaining method did not reveal significant differences, as the same as the apoptosis analysis. In conclusion, the coupling of L-Arg to Ibuprofen is an attractive alternative to Ibuprofen administration alone because it not only attenuates but also improves the evolution of chronic lesions through mechanisms that implicate endogenous PG and FGF-2-associated pathways, which allow an increase of angiogenesis process.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15736048&dopt=Abstract ibuprofen Motrin



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Incidence of outpatient physician claims for upper gastrointestinal symptoms among new users of celecoxib, ibuprofen, and naproxen in an insured population in the United States.

Goldstein JL, Zhao SZ, Burke TA, Palmer R, von Allmen H, Henderson SC.

Department of Medicine, Section of Digestive Diseases and Nutrition, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.

OBJECTIVE: The aim of this study was to compare the risk of outpatient medical claims for UGI symptoms among new users of celecoxib versus ibuprofen, and naproxen. METHODS: The study was conducted using LifeLink, an insurance claims database of approximately 1.8 million employees, dependents, and retirees in the United States. Patients newly treated with a prescription of celecoxib, ibuprofen, or naproxen between June 1, 1999, and June 30, 2001, were included. A patient with an upper GI (UGI) symptom was any individual with an outpatient physician claim for dyspepsia (ICD-9 = 536.8), abdominal pain (789.0), or nausea/vomiting (787.0). Incidence was determined using person-time analysis. Multivariate analyses were conducted using Poisson and Cox regression models. RESULTS: The cohort consisted of patients prescribed celecoxib (n = 68,939), ibuprofen (n = 71,456), or naproxen (n = 50,014). At baseline, celecoxib users were older and more likely to have a history of UGI or cardiovascular conditions. The incidence rate of any UGI symptom was 0.46 per 1,000 patient-days for celecoxib, 0.70 for ibuprofen, and 0.62 for naproxen. After adjusting for confounding factors using Poisson regression, the ibuprofen rate was 48% higher than the celecoxib rate (incidence rate ratio (IRR) = 1.48; 95% CI = 1.39-1.58; p < 0.001), whereas the naproxen rate was 40% higher (IRR = 1.40; 95% CI = 1.31-1.49; p < 0.001). The association between drug use and UGI symptoms was confirmed by Cox regression analysis; the hazard ratios were 1.21 (95% CI = 1.13-1.29; p < 0.001) for ibuprofen and 1.15 (95% CI = 1.07-1.23; p < 0.001) for naproxen relative to celecoxib. Younger age, female sex, medical history of UGI, cardiovascular and renal conditions, and higher baseline average healthcare expenditures for the 12-month period preceding the index prescription were also significantly associated with an increased incidence of UGI symptoms. CONCLUSIONS: Celecoxib use is associated with a significantly decreased risk of outpatient physician claims for UGI symptoms compared with commonly used prescription nonspecific nonsteroidal anti-inflammatory drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14687808&dopt=Abstract ibuprofen Motrin



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Effects of nonselective cyclooxygenase inhibition with low-dose ibuprofen on tumor growth, angiogenesis, metastasis, and survival in a mouse model of colorectal cancer.

Yao M, Zhou W, Sangha S, Albert A, Chang AJ, Liu TC, Wolfe MM.

Section of Gastroenterology, Boston University School of Medicine and Boston Medical Center, 650 Albany Street, Boston, MA 02118, USA.

PURPOSE: To determine whether the nonselective and relatively inexpensive nonsteroidal anti-inflammatory drug ibuprofen would be effective in inhibiting colorectal cancer and might improve mortality in a mouse model. EXPERIMENTAL DESIGN: The effects of ibuprofen on tumor growth inhibition and animal survival have been examined in both mouse and human colorectal cancer tumor models. Angiogenesis was measured by in vitro endothelial cell tube formation and immunohistochemistry. RESULTS: Ibuprofen significantly inhibited cell proliferation in mouse (MC-26) and human (HT-29) colorectal cancer cell lines. In vitro angiogenesis assays also indicated that ibuprofen decreased both cell proliferation and tube formation. The administration of chow containing 1,360 ppm ibuprofen, which achieved an average plasma concentration of ibuprofen lower than the peak level achieved in humans at therapeutic doses, inhibited tumor growth by 40% to 82%. Fewer liver metastases were found in the ibuprofen group compared with the control group. In combination therapy with the standard antineoplastic agents, 5-fluorouracil, or irinotecan (CPT-11), tumor volumes in the groups with ibuprofen +/- CPT-11 or 5-fluorouracil were smaller than in the control group. Ibuprofen was similar to the cyclooxygenase-2 selective inhibitor rofecoxib in its ability to suppress tumor growth and improve overall survival. CONCLUSIONS: Ibuprofen, in part by modulating tumor angiogenesis, decreases both tumor growth and metastatic potential in mice. The ibuprofen doses were in the low range of therapeutic human plasma concentrations. Ibuprofen potentiates the antitumor properties of CPT-11 and improves survival of mice without increasing gastrointestinal toxicity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15746067&dopt=Abstract ibuprofen Motrin