Motrin
The effect of the cyclooxygenase blockers, ibuprofen on the development of glomeruli in Sprague-Dawley rats.

Akinola O, Noronha C, Oremosu A, Kusemiju O, Okanlawon OA.

Department of Anatomy, College of Medicine, University of Lagos, P.M.B. 12003, Lagos, Nigeria.

Cyclo-oxygenase mediated prostaglandins are important determinants of glomerular development and kidney function. Ibuprofen inhibit the enzyme cyclo-oxygenase and thereby block the prostaglandin synthesis in the kidneys. Cyclo-oxygenase exist in two iso-forms (COX-1 and COX-2). It has ben proposed that Non-steroidal anti-inflammatory drugs (NSAIDs) with preferential COX-2 selectivity have fewer renal side effects than drugs with preferential COX-1 selectivity. The significance of this remains unclear since nephrotoxicity is relatively uncommon with ibuprofen and, when present is usually rapidly reversible although, ibuprofen has a higher potency against COX-1 than COX-2. We therefore investigated the effect of ibuprofen on glomerulogenesis in Sprague-Dawley rats. Ibuprofen (22 mg/kg/day) was administered orally from day 10 of gestation to day 15 after parturition. Light microscopic examination of ibuprofen-treated neonatal kidneys show hypoplastic glomeruli. These results suggest that low dose ibuprofen is deleterious to glomerular development.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12717465&dopt=Abstract ibuprofen Motrin



Motrin
Administration of the non-steroidal anti-inflammatory drug ibuprofen increases macrophage concentrations but reduces necrosis during modified muscle use.

Cheung EV, Tidball JG.

Department of Physiological Science, University of California, 5833 Life Science Building, Los Angeles, CA 90095-1524, USA.

OBJECTIVE: To test the hypothesis that ibuprofen administration during modified muscle use reduces muscle necrosis and invasion by select myeloid cell populations. METHODS: Rats were subjected to hindlimb unloading for 10 days, after which they experienced muscle reloading by normal weight-bearing to induce muscle inflammation and necrosis. Some animals received ibuprofen by intraperitoneal injection 8 h prior to the onset of muscle reloading, and then again at 8 and 16 h following the onset of reloading. Other animals received buffer injection at 8 h prior to reloading and then ibuprofen at 8 and 16 h following the onset of reloading. Control animals received buffer only at each time point. Quantitative immunohistochemical analysis was used to assess the presence of necrotic muscle fibers, total inflammatory infiltrate, neutrophils, ED1+ macrophages and ED2+ macrophages at 24 h following the onset of reloading. RESULT: Administration of ibuprofen beginning 8 h prior to reloading caused significant reduction in the concentration of necrotic fibers, but increased the concentration of inflammatory cells in muscle. The increase in inflammatory cells was attributable to a 2.6-fold increase in the concentration of ED2+ macrophages. Animals treated with ibuprofen 8 h following the onset of reloading showed no decrease in muscle necrosis or increase in ED2+ macrophage concentrations. CONCLUSION: Administration of ibuprofen prior to increased muscle loading reduces muscle damage, but increases the concentration of macrophages that express the ED2 antigen. The increase in ED2+ macrophage concentration and decrease in necrosis may be mechanistically related because ED2+ macrophages have been associated with muscle regeneration and repair.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12755383&dopt=Abstract ibuprofen Motrin



Motrin
Novel ibuprofen potentiometric membrane sensors based on tetraphenylporphyrinato indium(III).

Hassan SS, Mahmoud WH, Elmosallamy MA, Almarzooqi MH.

Department of Chemistry, Faculty of Science, Ain Shams University, Cairo, Egypt. saadsmhassan yahoo.com

Two novel potentiometric membrane sensors responsive to the ibuprofen drug have been developed. These incorporate poly(vinyl chloride) and polyurethane matrix membranes containing 5,10,15,20-tetraphenylporphrinato (TPP) indium(II) ionophore plasticized with dibutylsebacate. The sensors show a near-Nernstian response with anionic slopes of -53 and -55 mV decade(-1), over the concentration range of 4.2 x 10(-6)-1.0 x 10(-2) and 3.3 x 10(-6)-1.0 x 10(-2) M ibuprofen within pH ranges of 4-9 and 5-9 for PVC and PU matrix membranes, respectively. A sensor based on a polyurethane membrane displays a lower detection limit and a wider linear working range, and a sensor based on a PVC membrane exhibits a better overall selectivity, especially in the presence of lipophilic organic anions. Both sensors are used for the quantification and quality-control assessment of ibuprofen in pharmaceutical preparations. The average recoveries are 99.1+/-0.3% and 99.3+/-0.3% for TPP In(III)-PVC and TPP In(III)-PU based membrane sensors, respectively. High selectivities towards ibuprofen in the presence of many anions, drug excipients and diluents are offered by both sensors, which exhibit a non-Hofmeister selectivity pattern.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12769363&dopt=Abstract ibuprofen Motrin



Motrin
Modulation of inflammatory mediators by ibuprofen and curcumin treatment during chronic inflammation in rat.

Banerjee M, Tripathi LM, Srivastava VM, Puri A, Shukla R.

Division of Pharmacology, Central Drug Research Institute, Lucknow, India.

Inflammation is a protective tissue response occurring in three distinct phases, acute, subacute and a chronic proliferative phase. We undertook the present study to understand the overall immune response of the body during adjuvant induced chronic inflammation in rat and the effect of ibuprofen and curcumin on this response. Inflammatory mediators were estimated on day 21 and day 35 after adjuvant injection. The level of C-reactive protein increased to 200% on day 21 and then reduced to 50% on day 35 compared to control. Curcumin and ibuprofen further reduced the increased levels at both the time intervals. Haptoglobin level decreased to 42% on day 21 but increased to 5 times of control on day 35. Curcumin and ibuprofen reduced the increased levels at day 35. No significant change was observed in Prostaglandin-E2 and Leukotriene-B4 levels and in Lymphocyte proliferation. The level of Tumor Necrosis Factor-alpha increased by three folds on day 21, but came down to 88% on day 35. Ibuprofen treatment decreased the raised level on day 21 and increased the reduced level on day 35. Interleukin-1beta increased to 2 folds on day 21 and 10 folds on day 35 which were significantly brought down by curcumin and ibuprofen. Nitric oxide level was reduced at both the time intervals, which were increased by drug treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12784914&dopt=Abstract ibuprofen Motrin



Motrin
Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers.

Kolhe P, Misra E, Kannan RM, Kannan S, Lieh-Lai M.

Department of Chemical Engineering and Material Science, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA.

Highly branched, functionalized polymers have potential to act as efficient drug carrier systems. Dendrimers are ideal candidates among model hyperbranched polymers because of their well-defined structure and high density of functional groups. Using ibuprofen as a model drug, we studied the interaction between the drug and Polyamidoamine (PAMAM) dendrimers (generations 3 and 4 with --NH2 functionality) and Perstrop Polyol (generation 5, hyperbranched polyester with --OH functionality). FTIR and NMR studies suggest that ibuprofen predominantly forms a complex with PAMAM dendrimers because of the ionic interaction between the --NH2 end groups and the carboxyl group of ibuprofen. On an average, up to 78 molecules of ibuprofen could be incorporated into one molecule of PAMAM-G4-NH2 with 64 end groups. This complex is stable in deionized water and methanol. The in vitro release of ibuprofen from drug-dendrimer complex is appreciably slower compared to pure ibuprofen. The complexed drug enters A549 cells much more rapidly than pure drug suggesting that dendrimers may be able to carry the complexed drug inside cells efficiently. Hyperbranched Polyol (with 128 --OH end groups) appears to encapsulate approximately 24 drug molecules. Perhaps the lack of strong interactions between the --OH end groups and the drugs prevents complex formation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12787643&dopt=Abstract ibuprofen Motrin



Motrin
Short-term tests with a pilot sewage plant and biofilm reactors for the biological degradation of the pharmaceutical compounds clofibric acid, ibuprofen, and diclofenac.

Zwiener C, Frimmel FH.

Engler-Bunte-Institut, Water Chemistry, Universitat Karlsruhe (TH), Engler-Bunte-Ring 1, D-76131 Karlsruhe, Germany. christian.zwiener ciw.uni-karlsruhe.de

The biodegradation of three active compounds of pharmaceuticals clofibric acid, ibuprofen, and diclofenac was investigated in short-term tests with a pilot sewage plant (PSP) and biofilm reactors (BFR, oxic and anoxic) as model systems for municipal sewage treatment. The PSP was characterized with respect to mixing behavior, the BFR with respect to biofilm content and sorption of the pharmaceutical compounds. The short-term experiments were carried out for 55 h in the PSP and for 48 h in the BFR. The concentration of the pharmaceuticals was in the microgram per liter range in presence of readily biodegradable substances in the milligram per liter range. Therefore, a too short time period and too low concentration to promote adaption of the microorganisms were applied. Under the operating conditions applied the biodegradation of the lipid lowering agent clofibric acid and the analgesic agents ibuprofen and diclofenac in the oxic BFR resembled that in the PSP. Clofibric acid and diclofenac were not eliminated and reached a level of approximately 95% of their initial concentration, whereas the concentration of ibuprofen was decreased to approximately 40% in the PSP and to approximately 35% in the oxic BFR. Both systems showed, therefore, an inherent ability for ibuprofen biodegradation. Elimination in the anoxic BFR resulted in a decrease of the concentration of all three substances to values between 60 and 80% of their initial concentration. In contrast to the PSP acetone revealed as inhibitor in the BFR. In both systems acetone was not degraded in the short-term tests.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12798104&dopt=Abstract ibuprofen Motrin



Motrin
Synthesis and hydrolytic behaviour of 2-mercaptoethyl ibuprofenate-polyethylene glycol conjugate as a novel transdermal prodrug.

Davaran S, Rashidi MR, Hashemi M.

Drug Applied Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran.

Thiolated derivatives of ibuprofen and its polyethylene glycol ester were synthesized via condensation of 2-mercaptoethyl ibuprofenate with carboxy-terminated polyethylene glycol. The release of ibuprofen from this polymeric prodrug has been studied under conditions simulating those encountered in the skin. The polymeric prodrug of ibuprofen was found to undergo pH-dependent hydrolysis, ranging from negligible hydrolysis at pH 4 to 23.9% hydrolysis at pH 8.5 (15% at pH 7.4) after 48 h at 37 degrees C. The polymer-drug conjugate was subjected to enzymatic hydrolysis in human plasma. The polymer showed considerable enzymatic hydrolysis (68% after 48 h). The results showed that the polymeric prodrug model of non-steroidal anti-inflammatory drugs (NSAIDs) described here can be used in topical formulations of NSAIDs. It is expected that the novel thiol derivative will have both enhanced transdermal penetration and stability to oxidation which make it a suitable candidate for transdermal formulations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12803773&dopt=Abstract ibuprofen Motrin



Motrin
Influence of age on the enantiomeric disposition of ibuprofen in healthy volunteers.

Tan SC, Patel BK, Jackson SH, Swift CG, Hutt AJ.

Department of Pharmacy, King's College, London, UK.

AIMS: To determine the influence of age on the enantioselective disposition of ibuprofen in humans. METHODS: Healthy young (n = 16; aged 20-36 years) and elderly (n = 16; aged 66-84 years) volunteers were given a 400-mg oral dose of racemic ibuprofen, and blood and urine samples were collected for 24 h post drug administration. Serum concentrations, total and free, and urinary excretion of both enantiomers of ibuprofen together with the urinary excretion of the stereoisomers of the two major metabolites of the drug, both free and conjugated, were determined by high-performance liquid chromatography. RESULTS: Ageing had little effect on the distribution and metabolism of R-ibuprofen, unbound clearance of the R-enantiomer via inversion being approximately two-fold that via noninversion mechanisms in both age groups. In contrast, the free fraction of S-ibuprofen was significantly greater [33%; young 0.48 +/- 0.10%; elderly 0.64 +/- 0.20%] mean difference -0.16; 95% confidence interval (CI) -0.05, -0.27; P < 0.01; and the unbound clearance of the drug enantiomer was significantly lower (28%; young 15.9 +/- 2.2 l min-1; elderly 11.5 +/- 4.1 l min-1; mean difference 4.4; 95% CI 2.12, 6.68; P < 0.001) in the elderly. The metabolite formation clearances of S-ibuprofen via glucuronidation, and oxidation at the 2- and 3- positions of the isobutyl side chain decreased by 24, 28 and 30%, respectively, in the elderly compared with the young, the differences between the two age groups being significant in each case (P < 0.05). CONCLUSIONS: Following administration of racemic ibuprofen age-associated stereoselective alterations in drug disposition have been observed, with the elderly having increased free concentrations and lower unbound clearance of the S-enantiomer in comparison with the young. In contrast, the handling of the R-enantiomer is essentially unaltered with age. The results of this study indicate that the elderly have an increased exposure to the active ibuprofen enantiomer and thus some caution may be required when using this drug in this age group.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12814452&dopt=Abstract ibuprofen Motrin