Motrin
Pharmacokinetics of two new oral formulations of ibuprofen.

Benvenuti C, Cancellieri V, Gambaro V, Lodi F, Marozzi E, Scaroni C.

Two new formulations of ibuprofen were studied in 600 mg coated tablets and granules, to allow an easier adjustment of its daily dosage now higher than in the past. Six healthy volunteers (3M and 3F, mean age 32.6 years took part in a 6 X 6 Latin Square single dose pharmacokinetic study comparing six oral formulations of ibuprofen: 600 mg coated tablets, 300, 400 and 600 mg resinated granules, 300 and 400 mg sugar-coated tablets available on the market as Brufen. The results show that there is a correlation between dose and the area under the blood concentration-time curve. The availability of ibuprofen was similar irrespective of whether it is given in the form of granules or in tablets. The short half-life and the widespread use of ibuprofen give an acceptable range of safety to these new formulations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3733280&dopt=Abstract ibuprofen Motrin



Motrin
Protective effects of ibuprofen and methylprednisolone on chemotactic factor-induced transcutaneous hypoxia.

Maderazo EG, Breaux SP, Woronick CL.

We showed previously in vitro that ibuprofen, a nonsteroidal anti-inflammatory agent, at concentrations easily achievable in blood, inhibits polymorphonuclear leukocyte cell swelling and aggregation in response to chemotactic factor stimulation. To confirm this in vivo, we studied the ability of ibuprofen i.v. pretreatment to reverse the transcutaneous hypoxia induced by i.v. infusion of 1 nmol/kg of formyl-methionyl-leucyl-phenylalanine. This effect was compared with that of methylprednisolone. For ibuprofen and methylprednisolone, respectively, the maximum percentage of reversal of hypoxia was 85 and 106%; the dose required to produce 50% of maximum reversal was 2.7 and 4.6 mg/kg; and the serum drug concentration needed to achieve 50% of maximum reversal was 14 and 11 micrograms/ml. We conclude that ibuprofen could be a useful alternative to steroidal antiinflammatory agents for the prevention and treatment of complications of stimulated polymorphonuclear leukocytes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3735126&dopt=Abstract ibuprofen Motrin



Motrin
Reassessment of the in vitro synergistic effect of fluconazole with the non-steroidal anti-inflammatory agent ibuprofen against Candida albicans.

Arai R, Sugita T, Nishikawa A.

Department of Microbiology, Meiji Pharmaceutical University, Tokyo, Japan.

We reassessed the in vitro synergistic effect of fluconazole with the non-steroidal anti-inflammatory agent ibuprofen against the pathogenic yeast Candida albicans. No synergistic effect of fluconazole combined with ibuprofen was seen against fluconazole-susceptible strains, but a remarkable effect was seen against fluconazole-resistant strains (FIX index: 0.02-0.03). Furthermore, vigorous growth of the microorganism, the so-called 'Eagle effect', was observed at concentrations higher than the minimal inhibitory concentrations of ibuprofen and fluconazole. Our results suggest that the combination of ibuprofen and fluconazole should prove useful for treating infection caused by fluconazole-resistant C. albicans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15679664&dopt=Abstract ibuprofen Motrin



Motrin
Development of capillary gas chromatographic-mass spectrometric methodology for the simultaneous determination of ibuprofen and [ar-2H4]ibuprofen in serum: demonstration of kinetic equivalence in the beagle.

Theis DL, Halstead GW, Halm KA.

A capillary gas chromatographic-mass spectrometric method for the determination of ibuprofen and tetra-deuterated ibuprofen in serum is described. Ibuprofen, [ar-2H4]ibuprofen and the internal standard, [ar-2H4,3,3,3-2H3]ibuprofen, are extracted (after acidification) from serum onto a cross-linked styrene divinyl benzene resin by an automated sample processor. After elution and evaporation of the organic phase, samples are reconstituted with solvent and analyzed without derivatization by capillary gas chromatography-mass spectrometry. This methodology was used to evaluate possible kinetic isotope effects after the coadministration of an equimolar mixture of ibuprofen and the deuterium-labeled covariant in the beagle. No significant differences in absorption or elimination were observed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3745396&dopt=Abstract ibuprofen Motrin



Motrin
Increased viability and differentiation of normal and dystrophic striated muscle in vitro.

Walter RJ, Hyun J.

Primary cultures of muscle from normal (line 412) and dystrophic (line 413) chick embryos were exposed to corticosterone-21-acetate (C-21-A) or sodium ibuprofen (Motrin) for 28 d after myotube formation. Ibuprofen (0.5 to 500 micrograms/ml) or C-21-A (0.4 to 40 micrograms/ml)-treated cultures were fixed and assessed semiquantitatively using phase microscopy. On this basis, ibuprofen (50 micrograms/ml) and C-21-A (40 micrograms/ml) seemed to be effective in maintaining both normal and dystrophic muscle cultures. Using ibuprofen and C-21-A at these concentrations, experiments were repeated and analyzed quantitatively. Ibuprofen maintained culture viability (up to 68% more myotubes than untreated controls) but had no significant effect on the number of striated cells. C-21-A effectively maintained culture viability (up to 73% increase) and strongly promoted the formation of striated cells in these cultures (up to a sixfold increase). Both normal and dystrophic cultures were affected similarly by these agents, but the dystrophic cultures showed more consistent if not more extensive improvements in the parameters examined here. Thus, it seems that ibuprofen and C-21-A may affect both normal and dystrophic muscle directly to maintain survival and even promote differentiation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3759795&dopt=Abstract ibuprofen Motrin



Motrin
A critical comparison of the hematologic, cardiovascular, and pulmonary response to steroids and nonsteroidal anti-inflammatory drugs in a model of sepsis and adult respiratory distress syndrome.

Kopolovic R, Thraikill KM, Martin DT, Carey LC, Cloutier CT.

Improved survival of patients receiving high-dose steroid therapy in sepsis and adult respiratory distress syndrome (ARDS) has been reported, but such therapy and its benefits remain controversial. Recently research has been directed toward manipulation of the arachidonic acid cascade. Improved survival and hemodynamics with administration of nonsteroidal anti-inflammatory drugs (NSAID) have been reported in animal models of sepsis and ARDS. The purpose of this study was to compare the effects of steroids (methylprednisolone) and NSAID (ibuprofen) in a porcine model of septic ARDS induced by a continuous infusion of live Pseudomonas aeruginosa. Cardiopulmonary parameters were monitored in animals intubated, paralyzed, and ventilated at a 250 ml tidal volume and 0.5 Fio2. Pigs were randomly assigned to one of five groups: groups I and II received respective doses of 12.5 mg/kg ibuprofen and 30 mg/kg methylprednisolone at 20 and 210 minutes after baseline; group III had P. aeruginosa only; groups IV and V received respective doses of ibuprofen and methylprednisolone at 20 and 210 minutes of sepsis. Significant pulmonary edema, increased intrapulmonary shunting, hypoxemia, hemoconcentration, and systemic hypotension occurred with P. aeruginosa infusion. In septic animals treated with ibuprofen normal systemic arterial pressure was maintained, hemoconcentration was decreased, and oxygenation was improved with a significant decrease in shunting and pulmonary edema. Administration of methylprednisolone improved hemoconcentration and cardiac index, but no significant effect on pulmonary edema, intrapulmonary shunting, or oxygenation was observed. The results of this study demonstrated a significant beneficial effect of ibuprofen and we would encourage controlled clinical trials of this drug in the management of sepsis and ARDS. On the other hand, methylprednisolone was found to be relatively ineffective in treatment of circulatory collapse and ARDS associated with sepsis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3764692&dopt=Abstract ibuprofen Motrin



Motrin
Adhesion formation and uterine tube healing in the rabbit: a controlled study of the effect of ibuprofen and flurbiprofen.

Jarrett JC 2nd, Dawood MY.

To determine if the prostaglandin synthetase inhibitors ibuprofen and flurbiprofen can suppress postoperative adhesion formation, New Zealand White rabbits that had uterine tubal ligation underwent uterine tube reanastomosis and were given either saline solution (controls), 75 mg of ibuprofen intravenously every 6 hours, or 12.5 mg of flurbiprofen intravenously every 6 hours for 8 doses after operation. Both ibuprofen and flurbiprofen significantly reduced postoperative adhesions (p less than 0.025). With histologic indices of tissue reunion, ibuprofen and flurbiprofen were associated with significantly less scar thickness than controls (p less than 0.001) but did not have any significant effect on mucosal regeneration, foreign body reaction, and muscularis disruption. When all four histologic indices were compared, flurbiprofen but not ibuprofen had a significantly lower score than controls, indicating the greater potency of flurbiprofen over ibuprofen. Our findings show that ibuprofen and flurbiprofen can suppress perioperative and postoperative surgically induced inflammatory response associated with healing and thereby reduce adhesion formation and scar thickness.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3789032&dopt=Abstract ibuprofen Motrin



Motrin
Beneficial effects of ibuprofen on experimental microvascular free flaps: pharmacologic alteration of the no-reflow phenomenon.

Douglas B, Weinberg H, Song Y, Silverman DG.

Pharmacologic alteration of the no-reflow phenomenon was determined based on increased tolerance to ischemia in ibuprofen-treated free flaps. Sprague-Dawley rats (N = 60) were divided into control (lactated Ringer's) and treated (ibuprofen) groups and subdivided into six groups of ischemia: 1 hour, 6 hours, 8 hours, 10 hours, 12 hours, and 14 hours of ischemia. Fluorescein uptake was measured after 10, 30, and 60 minutes following microrevascularization. Dye elimination studies were done for each ischemia group that demonstrated good fluorescein uptake. All free flaps in the 1-, 6-, and 8-hour groups survived. The ibuprofen-treated 10- and 12-hour flaps all survived, whereas the 10-hour control and 14-hour ibuprofen-treated free flaps failed to survive. Despite high fluorescein uptake, the 14-hour ibuprofen-treated flaps did not eliminate the fluorescein, whereas all surviving free flaps adequately eliminated the fluorescein. Failure to eliminate dye despite adequate uptake suggested a deranged microcirculation with increasing ischemia time. By inhibiting cyclo-oxygenase, nonsteroidal anti-inflammatory agents such as ibuprofen may block the untoward effects mediated by thromboxane A2, such as vasoconstriction, microvasculature thrombus formation, and intravascular sludging. These effects are theorized in part to be responsible for the failure of a free flap to survive despite revascularization.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3823212&dopt=Abstract ibuprofen Motrin