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[Binding affinity of ibuprofen to collagen and other connective tissue components]

[Article in German]

Menzel EJ, Kolarz G.

Institut fur Immunologie der Universitat Wien, Osterreich.

In vitro binding of ibuprofen to various tissue components was studied to explain differences in tissue concentration after local application of ibuprofen cream (Dolgit Creme). Radioactive ibuprofen was incubated with human Collagen Type I to V, Elastine, bovine, Mouse-Laminin, and Matrigel of the mouse, respectively. In low concentrations--similar to plasmaconcentrations after percutaneous application of ibuprofen--a specific binding especially to Laminin and Collagen Type IV could be found. This finding possibly explains previous autoradiographic results, which showed higher concentrations of ibuprofen in connective tissue compared with fat and other surrounding tissues.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2357251&dopt=Abstract ibuprofen Motrin



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Pharmacokinetics of S(+)- and R(-)-ibuprofen in volunteers and first clinical experience of S(+)-ibuprofen in rheumatoid arthritis.

Geisslinger G, Schuster O, Stock KP, Loew D, Bach GL, Brune K.

Department of Pharmacology and Toxicology, University of Erlangen, FRG.

S(+)-, R(-)- or racemic ibuprofen was administered orally to volunteers in doses of 150 mg, 300 mg and 500 mg pure S(+)-, 300 mg pure R(-)- and 600 mg racemic ibuprofen. The pharmacokinetic parameters in humans showed that S(+)-ibuprofen was not inverted to R(-)-ibuprofen, whereas R(-)-ibuprofen was inverted to S(+)-ibuprofen to a variable degree. S(+)-ibuprofen and R(-)-ibuprofen given alone more rapidly reached significantly higher maximal plasma concentrations than after the same doses of the racemic compound. The elimination half-lives and clearance values for all three forms of ibuprofen were comparable. The mean residence time of S(+)-ibuprofen after R(-)- and racemic ibuprofen was significantly longer than after administration of the pure S(+)-enantiomer. Judged by the AUC, the bioavailability of S(+)-ibuprofen was independent of the dose within the range tested. Administration of S(+)-ibuprofen to 6 rheumatic patients showed that the pharmacokinetic behaviour of S(+)-ibuprofen in patients was similar to that found in volunteers. S(+)-ibuprofen proved to be an effective analgesic antirheumatic drug in the dose range 1 to 1.5 g/day.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2379535&dopt=Abstract ibuprofen Motrin



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High-performance liquid chromatographic determination of the stereoisomeric metabolites of ibuprofen.

Rudy AC, Anliker KS, Hall SD.

Department of Medicine, Indiana University Medical School, Wishard Memorial Hospital, Indianapolis 46202.

A stereospecific reversed-phase high-performance liquid chromatographic (HPLC) method has been developed to simultaneously quantitate the stereoisomers of the two major metabolites of ibuprofen: hydroxyibuprofen and carboxyibuprofen. The metabolites were derivatized with S-(alpha)-methylbenzylamine to form diastereomeric amides which were separated and quantified on a C8 column. The validity of the stereoselective assay was confirmed by comparison with a non-stereoselective HPLC method. The stereoselective assay was applied to the quantification of all the stereoisomeric ibuprofen metabolites in urine from human volunteers dosed with racemic ibuprofen or the individual enantiomers of ibuprofen. Significant substrate and product stereo-selectivities were observed in the formation of carboxyibuprofen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2384577&dopt=Abstract ibuprofen Motrin



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d-Ibuprofen in ocular inflammation induced by paracentesis of the rabbit eye.

Tjebbes GW, van Delft JL, Barthen ER, van Haeringen NJ.

Department of Ophthalmology, University of Leiden, The Netherlands.

The anti-inflammatory compound d-ibuprofen has been investigated for anti-inflammatory and cyclooxygenase inhibitory activity in ocular inflammation induced by paracentesis of eyes of living rabbits. d-Ibuprofen is the dextro-rotary isomer of ibuprofen, a potent non-steroidal anti-inflammatory agent. Eyes pretreated topically with d-ibuprofen 0.8% showed a significant inhibition of aqueous protein (73.0%) and prostaglandin E2 (96.4%) increase after paracentesis as compared to paracentesized untreated fellow eyes and control eyes. In aqueous humor no significant correlation between the increase in prostaglandin E2 and protein could be established after paracentesis. These results indicate that d-ibuprofen could be a useful ocular anti-inflammatory agent as cyclooxygenase inhibitor.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2389059&dopt=Abstract ibuprofen Motrin



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The effects of topical S(+)-ibuprofen on interleukin-1 induced ocular inflammation in a rabbit model.

Tilden ME, Boney RS, Goldenberg MM, Rosenbaum JT.

Department of Ophthalmology, Oregon Health Sciences University, Portland.

Topical non-steroidal anti-inflammatory drugs may serve as an alternative or adjunct to topical corticosteroid therapy for iritis. We have tested the efficacy of topically given S(+)-ibuprofen in a rabbit model of uveitis secondary to the intravitreal injection of human recombinant interleukin 1-alpha. Topically administered S(+)-ibuprofen was found to inhibit increased vascular permeability associated with this model. These results with topical S(+)-ibuprofen compare favorably to the results seen with topical prednisolone and are significantly superior to the results seen with topical flurbiprofen. Topical S(+)-ibuprofen did not significantly reduce the cellular infiltration associated with interleukin-1 induced inflammation. These findings suggest a potential role for topical S(+)-ibuprofen in the treatment of ocular inflammation and, in this animal model, it appears to be superior to an alternative non-steroidal compound, but further studies are indicated to assess its activity in alternate models of ocular inflammation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2394932&dopt=Abstract ibuprofen Motrin



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Metabolic chiral inversion of ibuprofen in isolated rat hepatocytes.

Muller S, Mayer JM, Etter JC, Testa B.

Ecole de Pharmacie, Universite de Lausanne, Switzerland.

Ibuprofen was used to demonstrate that isolated rat hepatocytes offer a suitable in vitro model to investigate the metabolic chiral inversion of anti-inflammatory 2-arylpropionic acids (profens). The inversion of the pharmacologically inactive (-)-(R)-ibuprofen to the active (+)-(S)-ibuprofen was shown to obey apparent first-order kinetics during 5 h and to increase linearly with increasing hepatocyte concentration up to 4 x 10(5) cells/ml. No elimination of (R)-ibuprofen by routes other than inversion was seen, whereas the elimination of (S)-ibuprofen appeared to be saturable.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2400640&dopt=Abstract ibuprofen Motrin



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Ibuprofen plus prostaglandin E1 in a septic porcine model of adult respiratory distress syndrome.

Davies EA, Campbell AJ 3rd, Devine MJ, Steinberg SM, Cloutier CT.

Department of Surgery, Ohio State University College of Medicine, Columbus.

Prostaglandin manipulation has been shown to improve pulmonary dysfunction in animal models of acute respiratory distress syndrome. Using our previously reported porcine model of Pseudomonas-induced respiratory failure, we examined the therapeutic effects of a vasodilating prostaglandin, PGE1, and a reversible cyclooxygenase inhibitor, ibuprofen. Forty-two animals were randomized to seven groups: I--ibuprofen; II--PGE1; III--ibuprofen + PGE1; IV--Pseudomonas + ibuprofen; V--Pseudomonas + PGE1; VI--Pseudomonas + ibuprofen + PGE1; VII--Pseudomonas. Ibuprofen significantly improved pulmonary vasoconstriction, pulmonary hypertension, and hypoxemia, as well as increased survival slightly. PGE1 had no effect on pulmonary dysfunction, but prevented the rise in systemic vascular resistance that occurred in untreated, infected animals and animals treated with ibuprofen alone. Combination therapy improved stroke volume index, a measure of nonpulmonary organ function.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2494356&dopt=Abstract ibuprofen Motrin



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Transdermal self-permeation enhancement of ibuprofen.

Al-Saidan SM.

Department of Pharmaceutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, SAFAT 13110, Kuwait. alsaidan hsc.edu.kw

The objective of this study was to prepare saturated solutions of ibuprofen, of different concentrations, and to investigate their effect on permeation of ibuprofen across rat epidermis. Ibuprofen saturated solutions were prepared using 0.1, 0.2, 0.3 and 0.4 M disodium hydrogen phosphate solution (DHP). The solubility of ibuprofen in DHP increased as the molarity of DHP increased. Thus the four saturated solutions of ibuprofen (0.1M-DHP-IBU, 0.2M-DHP-IBU, 0.3M-DHP-IBU and 0.4M-DHP-IBU) have different concentrations of the same drug, and showed same pH (pH 7.0+/-1). The permeability study was also carried out using human epidermis and silastic membrane. Permeation rate of ibuprofen across rat epidermis and human epidermis from 0.4M-DHP-IBU was much greater than from 0.1M-DHP-IBU. The magnitudes of increase in the drug flux were 46.4-fold with rat epidermis and 9.4-fold with human epidermis. Such a great increase in drug flux was not observed with silastic membrane, only 1.4-fold. This suggests that the increased drug flux is likely due to drug-skin interaction and not the increased concentration of ibuprofen per se. Surface tension (ST) measurements of DHP versus ibuprofen concentration showed ST reduction of DHP, from 72 to 27.9 dyn/cm. This is an indication that ibuprofen acted as ionic surfactant and the observed skin permeability enhancement is attributed to disruption of stratum corneum barrier. Results of DSC study supported this assumption. DSC of untreated rat stratum corneum samples showed lipid transitions at 41.9+/-0.0 degrees C (T1), 55.1+/-1.6 degrees C (T(x)), 70.2+/-0.1 degrees C (T2) and 77.5+/-0.1 degrees C (T3), while those pretreated with 0.4M-DHP-IBU did not show the first three lipid transitions. Also, pretreatment of rat epidermis with 0.4M-DHP-IBU enhanced permeation of diclofenac sodium greater than 1250-fold. This corroborates that ibuprofen not only enhances its own permeation but also that of other drugs, such as diclofenac sodium.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15544868&dopt=Abstract ibuprofen Motrin