The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Ann E Kitchen - One of the best experts on this subject based on the ideXlab platform.
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the pharmacology of Benoxaprofen 2 4 chlorophenyl α methyl 5 benzoxazole acetic acid lrcl 3794 a new compound with anti inflammatory activity apparently unrelated to inhibition of prostaglandin synthesis
Journal of Pharmacy and Pharmacology, 2011Co-Authors: C H Cashin, W Dawson, Ann E KitchenAbstract:Benoxaprofen is a potent and long-acting anti-inflammatory and antipyretic compound. Its anti-inflammatory activity has been demonstrated in carrageenan-induced oedema, in cellulose pellet granuloma and in both developing and established adjuvant arthritis tests in rats. Its antipyretic activity is greater than either aspirin or paracetamol in tests inducing pyrexia with yeast or ‘E’ pyrogen in rats and rabbits. Benoxaprofen has analgesic activity in tests where pain is accompanied by inflammation but not in other experimental models of pain. The weak prostaglandin synthetase inhibiting properties of this compound differentiate it from other acid anti-inflammatory compounds. The low ulcerogenic potential of Benoxaprofen seen in animal models may be related to its relative inability to inhibit PG synthetase.
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effects of the non steroidal anti inflammatory drug Benoxaprofen on leucocyte migration
Journal of Pharmacy and Pharmacology, 2011Co-Authors: S C R Meacock, Ann E KitchenAbstract:Possible modes of action of the anti-inflammatory drug, Benoxaprofen, have been explored. The drug caused inhibition of leucocyte migration, principally of mononuclear cells into the pleural cavity of rats undergoing carrageenan-induced pleurisy. Evidence was obtained from in vitro leucocyte migration and chemotaxis models that the drug acted directly on the mononuclear cells rather than by inhibition of chemotactic factors.
Leslie Z Benet - One of the best experts on this subject based on the ideXlab platform.
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stereoselective metabolism of Benoxaprofen in rats biliary excretion of Benoxaprofen taurine conjugate and glucuronide
Drug Metabolism and Disposition, 1998Co-Authors: Kiminori Mohri, Kenji Okada, Leslie Z BenetAbstract:Benoxaprofen (BOP) was administered iv to bile duct-cannulated rats at a dose of 10 mg/kg. BOP and its metabolites in plasma, urine, and bile were quantified using HPLC. A previously unidentified BOP metabolite was found in HPLC chromatograms of rat bile, and the metabolite was isolated chromatographically. Positive-ion fast-atom bombardment (FAB) MS analysis of the compound showed [M+H]+ at m/z 409, i.e. 108 mass units greater than the molecular weight of BOP (301 mass units). In the 1H NMR spectrum of the compound, two signals assigned to two methylene groups appeared at 2.53 ppm and 3. 30 ppm, in addition to BOP signals. Analysis of FAB mass spectra and 1H-1H and 1H-13C correlated NMR spectra of the isolated metabolite suggested that the new metabolite was a BOP taurine conjugate (BOP-T). A BOP-T standard was chemically synthesized, and physicochemical data were compared with those for the isolated metabolite. Identical results, i.e. RF values from TLC, RT values from HPLC, and FAB MS and 1H-13C correlated NMR findings, were obtained, establishing that the new metabolite found in rat bile was BOP-T. In five rats, mean values for per cent excretion of the dose in bile over 12 hr for BOP glucuronide (BOP-G), BOP-T, and unchanged BOP were 13.2 +/- 2.3, 2.54 +/- 0.80, and 0.33 +/- 0.09%, respectively. Furthermore, the optical isomers of BOP and its metabolites in plasma and bile were analyzed using a chiral HPLC column. (R)-BOP showed rapid plasma elimination, whereas the plasma elimination of (S)-BOP was very slow. The amounts of BOP, BOP-G, and BOP-T enantiomers excreted into the bile were as follows: (S)-BOP-G and (R)-BOP-G, 12.5 +/- 1.8 and 2.1 +/- 0.6% of the dose; (R)-BOP-T and (S)-BOP-T, 2.0 +/- 0.6 and 0.3 +/- 0.05% of the dose; (R)-BOP and (S)-BOP, 0.02 +/- 0.03 and 0.2 +/- 0.1% of the dose, respectively. (S)-BOP was metabolized mainly to BOP-G, and BOP-T excreted into the bile was produced mainly from (R)-BOP.
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mechanisms for covalent binding of Benoxaprofen glucuronide to human serum albumin studies by tandem mass spectrometry
Drug Metabolism and Disposition, 1998Co-Authors: Yongchang Qiu, Alma L Burlingame, Leslie Z BenetAbstract:Tandem MS has been used to establish the structure and specific binding sites of covalent protein adducts formed upon incubation of the acyl glucuronide of the propionic acid nonsteroidal anti-inflammatory drug Benoxaprofen with human serum albumin in vitro. Benoxaprofen 1-O-beta-glucuronide was enzymatically synthesized in vitro and incubated with human serum albumin both in the presence and in the absence of NaCNBH3. The modified human serum albumins were digested with trypsin and separated by HPLC. The modified peptides were detected using HPLC-electrospray MS (with selected-ion monitoring) and were structurally characterized by tandem MS using matrix-assisted laser desorption ionization in both the post-source decay and high-energy collision-induced dissociation modes. These studies established that Benoxaprofen glucuronide forms covalent adducts with protein nucleophiles both by nucleophilic displacement of glucuronic acid at the anomeric center and by condensation of the rearranged acyl glucuronic acid isomers with epsilon-amino functions of lysine residues after acyl migration of the aglycone from the anomeric center. Lys-159 was identified as the major binding site. Thus, we have established that members of the less reactive propionic acid class of acyl glucuronides, such as the glucuronide of Benoxaprofen, are also capable of reacting with protein nucleophiles to form covalent adducts analogous to those of tolmetin glucuronide (tolmetin is an acetic acid nonsteroidal anti-inflammatory drug), via the mechanisms previously reported from this laboratory, and that the specific covalent binding site profile appears to be drug dependent.
C H Cashin - One of the best experts on this subject based on the ideXlab platform.
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the pharmacology of Benoxaprofen 2 4 chlorophenyl α methyl 5 benzoxazole acetic acid lrcl 3794 a new compound with anti inflammatory activity apparently unrelated to inhibition of prostaglandin synthesis
Journal of Pharmacy and Pharmacology, 2011Co-Authors: C H Cashin, W Dawson, Ann E KitchenAbstract:Benoxaprofen is a potent and long-acting anti-inflammatory and antipyretic compound. Its anti-inflammatory activity has been demonstrated in carrageenan-induced oedema, in cellulose pellet granuloma and in both developing and established adjuvant arthritis tests in rats. Its antipyretic activity is greater than either aspirin or paracetamol in tests inducing pyrexia with yeast or ‘E’ pyrogen in rats and rabbits. Benoxaprofen has analgesic activity in tests where pain is accompanied by inflammation but not in other experimental models of pain. The weak prostaglandin synthetase inhibiting properties of this compound differentiate it from other acid anti-inflammatory compounds. The low ulcerogenic potential of Benoxaprofen seen in animal models may be related to its relative inability to inhibit PG synthetase.
S C R Meacock - One of the best experts on this subject based on the ideXlab platform.
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effects of the non steroidal anti inflammatory drug Benoxaprofen on leucocyte migration
Journal of Pharmacy and Pharmacology, 2011Co-Authors: S C R Meacock, Ann E KitchenAbstract:Possible modes of action of the anti-inflammatory drug, Benoxaprofen, have been explored. The drug caused inhibition of leucocyte migration, principally of mononuclear cells into the pleural cavity of rats undergoing carrageenan-induced pleurisy. Evidence was obtained from in vitro leucocyte migration and chemotaxis models that the drug acted directly on the mononuclear cells rather than by inhibition of chemotactic factors.
Yongchang Qiu - One of the best experts on this subject based on the ideXlab platform.
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mechanisms for covalent binding of Benoxaprofen glucuronide to human serum albumin studies by tandem mass spectrometry
Drug Metabolism and Disposition, 1998Co-Authors: Yongchang Qiu, Alma L Burlingame, Leslie Z BenetAbstract:Tandem MS has been used to establish the structure and specific binding sites of covalent protein adducts formed upon incubation of the acyl glucuronide of the propionic acid nonsteroidal anti-inflammatory drug Benoxaprofen with human serum albumin in vitro. Benoxaprofen 1-O-beta-glucuronide was enzymatically synthesized in vitro and incubated with human serum albumin both in the presence and in the absence of NaCNBH3. The modified human serum albumins were digested with trypsin and separated by HPLC. The modified peptides were detected using HPLC-electrospray MS (with selected-ion monitoring) and were structurally characterized by tandem MS using matrix-assisted laser desorption ionization in both the post-source decay and high-energy collision-induced dissociation modes. These studies established that Benoxaprofen glucuronide forms covalent adducts with protein nucleophiles both by nucleophilic displacement of glucuronic acid at the anomeric center and by condensation of the rearranged acyl glucuronic acid isomers with epsilon-amino functions of lysine residues after acyl migration of the aglycone from the anomeric center. Lys-159 was identified as the major binding site. Thus, we have established that members of the less reactive propionic acid class of acyl glucuronides, such as the glucuronide of Benoxaprofen, are also capable of reacting with protein nucleophiles to form covalent adducts analogous to those of tolmetin glucuronide (tolmetin is an acetic acid nonsteroidal anti-inflammatory drug), via the mechanisms previously reported from this laboratory, and that the specific covalent binding site profile appears to be drug dependent.