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Pharmacokinetics of ibuprofen enantiomers after single and repeated doses in man.

Oliary J, Tod M, Nicolas P, Petitjean O, Caille G.

Departement de Pharmacologie hospitaliere, Hopital Avicenne, Bobigny, France.

The pharmacokinetic parameters of ibuprofen enantiomers after a single 600 mg dose and repeated 3 x 400 mg doses of Nurofen were determined in 12 healthy volunteers. Terminal half-lives were similar for both enantiomers, but plasma levels of S-ibuprofen were higher than those of R-ibuprofen, due to the chiral inversion and differences in distribution and metabolism. Comparison of maximal concentrations and areas under the concentration vs time curves between the first and last doses for each enantiomer indicated linear pharmacokinetics with no time-dependency. A large inter-individual variability in the ratio of S- to R-ibuprofen average concentrations at steady-state was observed (mean +/- SD 1.89 +/- 0.89) and probably accounts for the known lack of correlation between racemic ibuprofen concentrations and therapeutic efficacy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1498267&dopt=Abstract ibuprofen Motrin



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Failure to reduce experimental myocardial infarct size with ibuprofen pre-treatment in rats.

Lal A, Sharma ML.

Department of Pharmacology, M.G.I.M.S., Distt. Wardha, Maharashtra State.

The prophylactic role of ibuprofen in experimental myocardial infarction has not been reported. Twenty-four rats pre-treated with ibuprofen (30 mg/kg), po, for 21 days were subjected to myocardial infarction by administration of isoprenaline hydrochloride (85 mg/kg), sc, on two consecutive days. An equal number of rats were given saline to serve as control. Heart specimens were taken for macroscopic and microscopic examination after 1 day, 5 days, 12 days and 21 days, following myocardial infarction. Ibuprofen pre-treatment caused a significant increase in infarct size at all the intervals studied (P less than 0.01), indicating that ibuprofen exerted a harmful effect in increasing the size of experimental myocardial infarction.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1506079&dopt=Abstract ibuprofen Motrin



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High-dose ibuprofen therapy associated with esophageal ulceration after pneumonectomy in a patient with cystic fibrosis: a case report.

Mackey JE, Anbar RD.

Department of Pediatrics, University Hospital, State University of New York Upstate Medical University, Syracuse, NY, USA. mackeryj upstate.edu

BACKGROUND: Lung disease in patients with cystic fibrosis is thought to develop as a result of airway inflammation, infection, and obstruction. Pulmonary therapies for cystic fibrosis that reduce airway inflammation include corticosteroids, rhDNase, antibiotics, and high-dose ibuprofen. Despite evidence that high-dose ibuprofen slows the progression of lung disease in patients with cystic fibrosis, many clinicians have chosen not to use this therapy because of concerns regarding potential side effects, especially gastrointestinal bleeding. However, studies have shown a low incidence of gastrointestinal ulceration and bleeding in patients with cystic fibrosis who have been treated with high-dose ibuprofen. CASE PRESENTATION: The described case illustrates a life-threatening upper gastrointestinal bleed that may have resulted from high-dose ibuprofen therapy in a patient with CF who had undergone a pneumonectomy. Mediastinal shift post-pneumonectomy distorted the patient's esophageal anatomy and may have caused decreased esophageal motility, which led to prolonged contact of the ibuprofen with the esophagus. The concentrated effect of the ibuprofen, as well as its systemic effects, probably contributed to the occurrence of the bleed in this patient. CONCLUSIONS: This report demonstrates that gastrointestinal tract anatomical abnormalities or dysmotility may be contraindications for therapy with high-dose ibuprofen in patients with cystic fibrosis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15363106&dopt=Abstract ibuprofen Motrin



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A comparison of indomethacin with ibuprofen on gastrointestinal mucosal integrity in conventional and germ-free rats.

Melarange R, Moore G, Blower PR, Coates ME, Ward FW, Ronaasen V.

SmithKline Beecham Pharmaceuticals, Harlow Essex, UK.

The effects of indomethacin and ibuprofen on gastrointestinal mucosal integrity were studied in conventional and germ-free rats. Only ibuprofen induced significant gastric erosion formation in both conventional and germ-free animals, demonstrating that the presence of micro-organisms is not required in this form of damage. Both indomethacin and ibuprofen caused significant intestinal damage and blood loss in germ-free animals. However, in the conventional counterparts, damage due to indomethacin was enhanced whereas that induced by ibuprofen was not. The results from the present work would suggest that non-steroidal anti-inflammatory drugs such as indomethacin, which are secreted largely in the bile, unlike ibuprofen, may act in concert with bacteria and the constituents of bile to induce, in part, intestinal damage and blood loss.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1543817&dopt=Abstract ibuprofen Motrin



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Pharmaceutical evaluation of ibuprofen fast-absorbed syrup containing low-molecular-weight gelatin.

Kimura S, Imai T, Ueno M, Otagiri M.

Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.

Two kinds of ibuprofen syrups were prepared and evaluated. One was a suspending syrup, prepared by using hydroxypropyl methylcellulose (HPMC) as a dispersing agent, and the other was a dry syrup containing low-molecular-weight gelatin (LM gelatin). The dissolution behaviors of ibuprofen from syrups were studied, and both syrups showed size-dependent dissolution; the smaller particles exhibited faster dissolution. The in vivo absorption behaviors of the syrups were compared with that of commercial tablets of ibuprofen in beagle dogs and human volunteers. The absorption rates following oral administrations of syrups were much greater than those following administration of commercial tablets. Moreover, both syrups reduced the bitter taste and irritation of the oral mucosa caused by ibuprofen; the dry syrup markedly masked these side effects. These results suggest that the dry syrup containing LM gelatin improves some of the pharmaceutical properties of ibuprofen, and that the LM gelatin may be used in a variety of oral dosage forms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1545352&dopt=Abstract ibuprofen Motrin



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Interactions of ibuprofen with influenza infection and hyperammonemia in an animal model of Reye's syndrome.

Mukhopadhyay A, Sarnaik AP, Deshmukh DR.

Department of Pediatrics, Children's Hospital of Michigan, Detroit 48201.

We have previously reported that a single meal of an arginine-free diet rapidly induces hyperammonemia in young ferrets and that aspirin administration in conjunction with influenza B infection and arginine-free diet results in clinical and biochemical alterations consistent with Reye's syndrome. The objective of the present study was to test whether ibuprofen administration, either alone or in combination with influenza infection and arginine-free diet, produces a similar effect. Two-mo-old ferrets were inoculated intranasally with influenza B virus, treated with therapeutic doses of ibuprofen, and fed a single meal of an arginine-free diet. Arginine-free diet caused a significant increase in plasma ammonia and a small increase in plasma aspartate aminotransferase activity. All ferrets fed an arginine-free diet recovered within 6 to 7 h after ingesting the diet. Ibuprofen treatment, either solely or in combination with influenza infection, did not produce significant change in the plasma levels of aspartate or ornithine aminotransferase activities. A combination of ibuprofen treatment, influenza infection, and arginine-free diet caused a significant increase in the mortality and plasma ammonia levels. Plasma aspartate aminotransferase and ornithine carbamyl transferase activities were elevated, and liver ornithine carbamyl transferase activity was decreased. However, other mitochondrial enzymes such as ornithine aminotransferase were not altered, whereas the activity of cytoplasmic enzymes such as arginase were decreased. These results suggest that ibuprofen administration resulted in generalized hepatopathy rather than specific mitochondrial injury and Reye's syndrome-like changes associated with aspirin in our previous model.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1561011&dopt=Abstract ibuprofen Motrin



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Single-dose pharmacokinetics of ibuprofen and acetaminophen in febrile children.

Brown RD, Wilson JT, Kearns GL, Eichler VF, Johnson VA, Bertrand KM.

Department of Pharmacology & Therapeutics, Louisiana State University Medical Center, Shreveport 71130.

The disposition of antipyretic drugs is central to the understanding of their action in children. Accordingly, the authors measured plasma levels of acetaminophen and ibuprofen in 153 febrile children for 6 hours after a single dose of either acetaminophen (12.5 mg/kg) or ibuprofen (5 or 10 mg/kg). Cmax occurred about 2 1/2 hours before maximum antipyresis, when plasma acetaminophen or ibuprofen was 25 to 50% less than Cmax. Most plasma level data fit a one-compartment open model, and this suggests a pharmacodynamic basis for the observed lag between Cmax and maximum antipyretic response. Plasma levels (and AUCO----infinity) of ibuprofen 10 mg/kg were less than expected for a two-fold increase in dose. For acetaminophen, the tlag was less than ibuprofen, Ka was more than ibuprofen, and beta was less than ibuprofen. The ibuprofen beta was not dose dependent, but the Vd was dose and model dependent. In contrast, ibuprofen Clp was dose and model independent. Acetaminophen pharmacokinetics were similar to those previously reported. Initial temperature, race, gender, prior medications, or diagnosis did not confound the results for ibuprofen or acetaminophen. Accordingly, a pharmacodynamic basis is a more likely explanation for the initial temperature effects found previously for antipyretic drugs in children. Ibuprofen (5 and 10 mg/kg) AUCO-----infinity was higher in the older (greater than or equal to 2.5 yrs) children and the Vd and Clp were lower in the older children, when discriminated by age or pharmacokinetic parameters. The observed dose dependency of AUCO----infinity and the effect of age on ibuprofen disposition must be considered if pharmacokinetic interpretations are used to develop the antipyretic dose of ibuprofen in children.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1564127&dopt=Abstract ibuprofen Motrin



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Ibuprofen reduces ethchlorvynol lung injury: possible role of blood flow distribution.

Yagi K, Baudendistel LJ, Dahms TE.

Department of Anesthesiology, St. Louis University School of Medicine, St. Louis 63110.

The role of cyclooxygenase products in acute lung injury was determined by pretreatment of dogs with ibuprofen before injury with intravenous ethchlovynol (ECV). In animals given ECV only, lung injury resulted in extravascular lung water of 18.9 ml/kg after 2 h, which was significantly higher than the 14.8 ml/kg in the group pretreated with ibuprofen. The comparison of gravimetric and indicator-dilution measurements of edema fluid indicates that edema fluid could not be reliably detected after treatment with ibuprofen because of diversion of flow from injured areas. Venous admixture increased from 6% at baseline to 32% 120 min after ECV in the vehicle-pretreated group compared with an increase from 4% at baseline to 7% in the ibuprofen-pretreated group. The regression analysis of the relationship between venous admixture and extravascular lung water indicated that, at any level of edema, venous admixture was significantly less in the group treated with ibuprofen than in the untreated group. Measurement of plasma and bronchoalveolar lavage fluid indicated that ibuprofen inhibited cyclooxygenase activity without affecting lipoxygenase activity. These results suggest that in intact dogs ibuprofen has a protective effect on both pulmonary gas transfer and pulmonary edema formation in ECV-injured lungs, which is consistent with limiting blood flow to injured segments of the lung.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1568970&dopt=Abstract ibuprofen Motrin