Enantioselective pharmacokinetics of ibuprofen and involved mechanisms

Drug Metabolism Reviews

Volumn 37, Issue 1, 2005, Pages 215-234

  Hao, Haiping ^a   Wang, Guangji ^a   Sun, Jianguo ^a  

^a CHINA PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

Biochemical mechanisms; Enantioselective pharmacokinetics; Gene polymorphism; Ibuprofen; NSAIDs

Indexed keywords

ARYLPROPIONIC ACID DERIVATIVE; CARBOXYL GROUP; CYTOCHROME P450; CYTOCHROME P450 2C19; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; DEXIBUPROFEN; FLURBIPROFEN; IBUPROFEN; KETOPROFEN; NONSTEROID ANTIINFLAMMATORY AGENT; PRANOPROFEN;

AUSTRIA; CHIRALITY; DNA POLYMORPHISM; DRUG ABSORPTION; DRUG CLEARANCE; DRUG EXCRETION; DRUG HYDROXYLATION; DRUG MARKETING; DRUG MECHANISM; DRUG METABOLISM; DRUG PROTEIN BINDING; ENANTIOMER; ENANTIOSELECTIVITY; HUMAN; MOUSE; NONHUMAN; REVIEW; SWITZERLAND;

EID: 13844250391     PISSN: 03602532     EISSN: None     Source Type: Journal    
DOI: 10.1081/DMR-200047999     Document Type: Review

References (102)

1. Aboul-Enein, H. Y., Van Overbeke, A., Vander Weken, G., Baeyens, W., Oda, H., Deprez, P., De Kruif, A. (1998). HPLC on Chiralcel OJ-R for enantiomer separation and analysis of ketoprofen, from horse plasma, as the 9-aminophenanthrene derivative. J. Pharm. Pharmacol. 50(3):291-296.
2. Adam, S. S., Cliffe, E. E., Dickinoson, W., Nicholson, J. S. (1967). Some biological properties of 2-(-4-isobutylphenyl)-propionic acid. J. Pharm. Sci. 56:1686.
3. Ahn, H. Y., Jamali, F., Cox, S. R., Kittayanond, D., Smith, D. E. (1991). Stereoselective disposition of ibuprofen enantiomers in the isolated perfused rat kidney. Pharm. Res. 8(12):1520-1524.
4. Andrisano, V., Booth, T. D., Cavrini, V., Wainer, I. W. (1997). Enantioselective separation of chiral arylcarboxylic acids on an immobilized human serum albumin chiral stationary phase. Chirality 9(2):178-183.
5. Baillie, T. A., Adams, W. J., Kaiser, D. G., Olanoff, L. S., Halstead, G. W., Harpootlian, H., Van Giessen, G. J. (1989). Mechanistic studies of the metabolic chiral inversion of (R)-ibuprofen in humans. J. Pharmacol. Exp. Ther. 249(2):517-523.
6. Bhushan, R. (1998). Resolution of enantiomers of ibuprofen by liquid chromatography: a review. J. Biomed. Chromatogr. 12(6):309-316.
7. Bonato, P. S., Del Lama, M. P., de Carvalho, R. (2003). Enantioselective determination of ibuprofen in plasma by high-performance liquid chromatography-electrospray mass spectrometry. J. Chromatogr., B. Anal. Technol. Biomed. Life Sci. 796(2):413-420.
8. Brenner, S. S., Herrlinger, C., Dilger, K., Murdter, T. E., Hofmann, U., Marx, C., Klotz, U. (2003). Influence of age and cytochrome P450 2C9 genotype on the steady-state disposition of diclofenac and celecoxib. Clin. Pharmacokinet. 42(3):283-292.
9. Bronfman, M., Leighton, F. (1984). Carnitine acyltransferase and acyl-coenzyme a hydrolase activities in human liver. Quantitative analysis of their subcellular localization. Biochem. J. 224(3):721-730.
10. Brugger, R., Garcia Alia, B., Reichel, C., Waibel, R., Menzel, S., Brune, K., Geisslinger, G. (1996). Isolation and characterization of rat liver microsomal R-ibuprofenoyl-CoA synthetase. Biochem. Pharmacol. 52(7):1007-1013.
11. Bruggera, R., Reichel, C., Garcia Alia, B., Brune, K., Yamamoto, T., Tegeder, I., Geisslinger, G. (2001). Expression of rat liver long-chain acyl-CoA synthetase and characterization of its role in the metabolism of R-ibuprofen and other fatty acid-like xenobiotics. Biochem. Pharmacol. 61(6):651-656.
12. Caldwell, J., Hutt, A. J., Fournel-Gigleux, S. (1988). The metabolic chiral inversion and dispositional enantioselectivity of the 2-arylpropionic acids and their biological consequences. Biochem. Pharmacol. 37(1):105-114.
13. Castro, E., Soraci, A., Fogel, F., Tapia, O. (2000). Chiral inversion of R(-) fenoprofen and ketoprofen enantiomers in cats. J. Vet. Pharmacol. Ther. 23(5):265-271.
14. Chen, C. S., Chen, T., Shieh, W. R. (1990). Metabolic stereoisomeric inversion of 2-arylpropionic acids. On the mechanism of ibuprofen epimerization in rats. Biochim. Biophys. Acta 1033(1):1-6.
15. Chen, C. S., Shieh, W. R., Lu, P. H., Harriman, S., Chen, C. Y. (1991). Metabolic stereoisomeric inversion of ibuprofen in mammals. Biochim. Biophys. Acta 1078(3):411-417.
16. Chen, H., Zhang, S. M., Hernan, M. A., Schwarzschild, M. A., Willett, W. C., Colditz, G. A., Speizer, F. E., Ascherio, A. (2003). Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch. Neurol. 60(8):1059-1064.
17. Cox, S. R. (1988). Effect of route of administration on the chiral inversion of R(-)ibuprofen. Clin. Pharmacol. Ther. 43(2):146.
18. Cox, P. G., Moons, W. M., Russel, F. G., van Ginneken, C. A. (1991). Renal handling and effects of S(+)-ibuprofen and R(-)-ibuprofen in the rat isolated perfused kidney. Br. J. Pharmacol. 103(2):1542-1546.
19. Dai, D., Zeldin, D. C., Blaisdell, J. A., Chanas, B., Coulter, S. J., Ghanayem, B. I., Goldstein, J. A. (2001). Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid. Pharmacogenetics 11(7):597-607.
20. Davies, N. M. (1998). Clinical pharmacokinetics of ibuprofen. The first 30 years. Clin. Pharmacokinet. 34(2):101-154.
21. Doki, K., Hayakawa, T., Lin, W., Yanaguimoto, H., Ding, G., Inotsume, N. (2003). Effects of absorption rate on the pre-systemic chiral inversion of ibuprofen in rabbits. J. Pharm. Pharmacol. 55(8):1091-1097.
22. Fujino, T., Yamamoto, T. (1992). Cloning and functional expression of a novel long chain acyl-CoA synthetase expressed in brain. J. Biochem. 111(2):197-203.
23. Fujino, T., Kang, M. J., Suzuki, H., Iijima, H., Yamamoto, T. T. (1996). Molecular characterization and expression of acyl-CoA synthetase 3. J. Biol.Chem. 271(28):16748-16752.
24. Gaedigk, A., Casley, W. L., Tyndale, R. F., Sellers, E. M., Jurima-Romet, M., Leeder, J. S. (2001). Cytochrome P4502C9 (CYP2C9) allele frequencies in Canadian native Indian and inuit populations. Can. J. Physiol. Pharm. 79(10):841-847.
25. Garcia-Martin, E., Martinez, C., Tabares, B., Frias, J., Agundez, J. A. (2004). Interindividual variability in ibuprofen pharmacokinetics is related to interaction of cytochrome P450 2C8 and 2C9 amino acid polymorphisms. Clin. Pharmacol. Ther. 76(2):119-127.
26. Ghosh, B., Barbosa, E., Singh, I. (1995). Molecular cloning and sequencing of human palmitoyl-CoA ligase and its tissue specific expression. Mol. Cell. Biochem. 151(1):77-81.
27. Glowka, F. K., Karazniewicz, M. (2004). High performance capillary electrophoresis for determination of the enantiomers of 2-arylpropionic acid derivatives in human serum. Pharmacokinetic studies of ketoprofen enantiomers following administration of standard and sustained release tablets. J. Pharm. Biomed. Anal. 35(4):807-816.
28. Hall, S. D., Rudy, A. C., Knight, P. M., Brater, D. C. (1993). Lack of presystemic inversion of R-to S-ibuprofen in humans. Clin. Pharmacol. Ther. 53(4):393-400.
29. Hamman, M. A., Thompson, G. A., Hall, S. D. (1997). Regioselective and stereoselective metabolism of ibuprofen by human cytochrome P450 2C. Biochem. Pharmacol. 54(1):33-41.
30. Hilton, M. J., Thomas, K. V. (2003). Determination of selected human pharmaceutical compounds in effluent and surface water samples by high-performance liquid chromatography-electrospray tandem mass spectrometry. J. Chromatogr., A 1015(1-2):129-141.
31. International Ibuprofen Foundation. (2004). The story of ibuprofen. http://www.ibuprofen-foundation.com/what-ibuprofen/story.htm. (accessed on Aug 8, 2004).
32. Hutt, A. J., Caldwell, J. (1983). The metabolic chiral inversion of 2-arylpropionic acids - a novel route with pharmacological consequences. J. Pharm. Pharmacol. 35(11):693-704.
33. Imai, T., Nomura, T., Aso, M., Otagiri, M. (2003). Enantiospecific disposition of pranoprofen in beagle dogs and rats. Chirality 15(4):312-317.
34. Itoh, T., Saura, Y., Tsuda, Y., Yamada, H. (1997). Stereoselectivity and enantiomer-enantiomer interactions in the binding of ibuprofen to human serum albumin. Chirality 9(7):643-649.
35. Jabor, V. A., Lanchote, V. L., Bonato, P. S. (2002). Enantioselective analysis of ibuprofen in human plasma by anionic cyclodextrin-modified electrokinetic chromatography. Electrophoresis 23(17):3041-3047.
36. Jamali, F., Mehvar, A. S., Russell, S., Sattari, W., Yakimets, W., Koo, J. (1992). Human pharmacokinetics of ibuprofen enantiomers following different doses and formulations: intestinal chiral inversion. J. Pharm. Sci. 81(3):221-225.
37. Jamali, F., Lovlin, R., Aberg, G. (1997). Bi-directional chiral inversion of ketoprofen in CD-1 mice. Chirality 9(1):29-31.
38. Jeffrey, P., Tucker, G. T., Bye, A., Crewe, K. H., Wright, P. A. (1991). The site of inversion of R(-)-ibuprofen: Studies using rat in-situ isolated perfused intestine/liver preparations. J. Pharm. Pharmacol. 43:715-720.
39. Kaiser, D. G., Van Giessen, G. J., Resischer, R. J., Wechter, W. J. (1976). Isomeric inversion of ibuprofen (R)-enantiomer in humans. J. Pharm. Sci. 65(2):269-273.
40. Kamataki, T., Fujita, K., Nakayama, K., Yamazaki, Y., Miyamoto, M., Ariyoshi, N. (2002). Role of human cytochrome P450 (CYP) in the metabolic activation of nitrosamine derivatives: application of genetically engineered Salmonella expressing human CYP. Drug Metab. Rev. 34(3):667-676.
41. Kang, M. J., Fujino, T., Sasano, H., Minekura, H., Yabuki, N., Nargra, H., Iijima, H., Yamamoto, T. T. (1997). A novel arachidonate-preferring acyl-CoA synthetase is present in steroidogenic cells of rat adrenal, ovary, and testis. Proc. Natl. Acad. Sci. U. S. A. 94(7):2880-2884.
42. Kirchheiner, J., Meineke, I., Freytag, G., Meisel, C., Roots, I., Brockmoller, J. (2002). Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2. Clin. Pharmacol. Ther. 72(1):62-75.
43. Knadler, M. P., Hall, S. D. (1990). Stereoselective arylpropionyl-CoA thioester formation in vitro. Chirality 2(2):67-73.
44. Knights, K. M., Drogemuller, C. J. (2000). Xenobiotic-CoA ligases: kinetic and molecular characterization. Curr. Drug Metab. 1(1):49-66.
45. Knights, K. M., Jones, M. E. (1992). Inhibition kinetics of hepatic microsomal long chain fatty acid-CoA ligase by 2-arylpropionic acid non-steroidal anti-inflammatory drugs. Biochem. Pharmacol. 43(7):1465-1471.
46. Knihinicki, R. D., Williams, K. M., Day, R. O. (1989). Chiral inversion of 2-arylpropionic acid non-steroidal anti-inflammatory drugs - 1. In vitro studies of ibuprofen and flurbiprofen. Biochem. Pharmacol. 38(24):4389-4395.
47. La, S., Kim, J., Kim, J. H., Goto, J., Kim, K. R. (2003). Simultaneous chiral discrimination of multiple profens by cyclodextrin-modified capillary electrophoresis in normal and reversed polarity modes. Electrophoresis 24(15):2642-2649.
48. Lagrange, F., Penhourcq, F., Matoga, M., Bannwarth, B. (2000). Binding of ketoprofen enantiomers in various human albumin preparations. J. Pharm. Biomed. Anal. 23(5):793-802.
49. Legen, I., Zakelj, S., Kristl, A. (2003). Polarised transport of monocarboxylic acid type drugs across rat jejunum in vitro: the effect of mucolysis and ATP-depletion. Int. J. Pharm. 256(1-2):161-166.
50. Mayer, J. M. (1990). Stereoselective metabolism of anti-inflammatory 2-arylpropionates. Acta Pharm. Nord. 2(3):197-216.
51. Mayer, J. M., Bartolucci, C., Martre, J., Testa, B. (1988). Metabolic chiral inversion of anti-inflammatory 2-arylpropionionates: lack of reaction in liver homogenate and study of methine proton acidity. Xenobiotica 18(5):533-543.
52. McGinnity, D. F., Parker, A. J., Soars, M., Riley, R. J. (2000). Automated definition of the enzymology of drug oxidation by the major human drug metabolizing cytochrome P450s. Drug Metab. Dispos. 28(11):1327-1334.
53. Menzel, S., Beck, W. S., Brune, K., Geisslinger, G. (1993). Stereoselectivity of biliary excretion of 2-arylpropionates in rats. Chirality 5(6):422-427.
54. Menzel, S., Waibel, R., Brune, K., Geisslinger, G. (1994). Is the formation of R-ibuprofenyl-adenylate the first stereoselective step of chiral inversion. Biochem. Pharmacol. 48(5):1056-1058.
55. Menzel-Soglowek, S., Geisslinger, G., Brune, K. (1990). Stereoselective high-performance liquid chromatographic determination of ketoprofen, ibuprofen and fenoprofen in plasma using a chiral alpha 1-acid glycoprotein column. J. Chromatogr. 532(2):295-303.
56. Mills, R. F. N., Adam, S. S., Cliffe, E. E., Dickinoson, W., Nicholson, J. S. (1973). The metabolism of ibuprofen. Xenobiotica 3(9):589-598.
57. Minekura, H., Fujino, T., Kang, M. J., Fujita, T., Endo, Y., Yamamoto, T. (1997). Human acyl-coenzyme A synthetase 3 cDNA and localization of its gene (ACS3) to chromosome band 2q34-q35. Genomics 42(1):180-181.
58. Mullangi, R., Yao, M., Srinivas, N. R. (2003). Resolution of enantiomers of ketoprofen by HPLC: a review. Biomed. Chromatogr. 17(7):423-434.
59. Naidong, W., Lee, J. W. (1994). Development and validation of a liquid chromatographic method for the quantitation of ibuprofen enantiomers in human plasma. J. Pharm. Biomed. Anal. 12(4):551-556.
60. Nakajima, M., Fujiki, Y., Noda, K., Ohtsuka, H., Ohkuni, H., Kyo, S., Inoue, M., Kuroiwa, Y., Yokoi, T. (2003). Genetic polymorphisms of CYP2C8 in Japanese population. Drug Metab. Dispos. 31(6):687-690.
61. Nakamura, Y., Yamaguchi, T., Takahashi, S., Hahimoto, S., Iwatani, K., Nakagawa, Y. (1981). Optical isomerization mechanisms of R(-)-hydratropic acid derivatives. J. Pharmacobio-Dyn. S-1.
62. Ogihara, T., Tamai, I., Takanaga, H., Sai, Y., Tsuji, A. (1996). Stereoselective and carrier-mediated transport of monocarboxylic acids across Caco-2 cells. Pharm. Res. 13(12):1828-1832.
63. Paliwal, J. K., Smith, D. E., Cox, S. R., Berardi, R. R., Dunn-Kucharski, V. A., Elta, G. H. (1993). Stereoselective, competitive, and nonlinear plasma protein binding of ibuprofen enantiomers as determined in vivo in healthy subjects. J. Pharmacokinet. Biopharm. 21(2):145-161.
64. Patel, B. K., Jackson, S. H., Swift, C. G., Hutt, A. J. (2003). Disposition of flurbiprofen in man: influence of stereochemistry and age. Xenobiotica 33(10):1043-1057.
65. Piccini, M., Vitelli, F., Bruttini, M., Pober, B. R., Jonsson, J. J., Villanova, M., Zollo, M., Borsani, G., Ballabio, A., Renieri, A. (1998). FACL4, a new gene encoding long-chain acyl-CoA synthetase 4, is deleted in a family with Alportt syndrome, elliptocytosis, and mental retardation. Genomics 47(3):350-358.
66. Reichel, C., Bang, H., Brune, K., Geisslinger, G., Menzel, S. (1995). 2-Arylpropionyl-CoA epimerase: partial peptide sequences and tissue localization. Biochem. Pharmacol. 50(11):1803-1806.
67. Reichel, C., Brugger, R., Bang, H., Geisslinnger, G., Brune, K. (1997). Molecular cloning and expression of a 2-arylpropionyl-coenzyme a epimerase: a key enzyme in the inversion metabolism of ibuprofen. Mol. Pharmacol. 51(4):576-582.
68. Rettie, A. E., Haining, R. L., Bajpai, M., Levy, R. H. (1999). A common genetic basis for idiosyncratic toxicity of warfarin and phenytoin. Epilepsy Res. 35:253-255.
69. Roberts, B. J., Knights, K. M. (1992). Inhibition of rat peroxisomal palmitoyl-CoA ligase by xenobiotic carboxylic acids. Biochem. Pharmacol. 44(2):261-267.
70. Roberts, B. J., MacLeod, J. K., Singh, I., Knights, K. M. (1995). Kinetic characteristics of rat liver peroxisomal nafenopin-CoA ligase. Biochem. Pharmacol. 49(9):1335-1339.
71. Rudy, A. C., Knight, P. M., Brater, D. C., Hall, S. D. (1992). Stereoselective metabolism of ibuprofen in humans: administration of R-, S- and racemic ibuprofen. J. Pharmacol. Exp. Ther. 260(3):1456.
72. Rudy, A. C., Liu, Y., Brater, C., Hall, S. D. (1998). Stereoselective pharmacokinetics and inversion of (R)-ketoprofen in healthy volunteers. J. Clin. Pharmacol. 38(2 Suppl):3S-10S.
73. Sattari, S., Jamali, F. (1994). Evidence of absorption rate dependency of ibuprofen inversion in the rat. Chirality 6(5):435-439.
74. Sattari, S., Jamali, F. (1997). Involvement of the rat gut epithelial and muscular layer, and microflora in chiral inversion and acyl-glucuronidation of R-fenoprofen. Eur. J. Drug Metab. Pharmacokinet. 22(2):97-101.
75. Schneider, H. T., Nuernberg, B., Dietzel, K., Brune, K. (1990). Biliary elimination of non-steroidal anti-inflammatory drugs in patients. Br. J. Clin. Pharmacol. 29(1):123-127.
76. Schwarz, U. I. (2003). Clinical relevance of genetic polymorphisms in the human CYP2C9 gene. Eur. J. Clin. Investig. 33(Suppl 2):23-30.
77. Seideman, P., Lohrer, F., Graham, G. G., Duncan, M. W., Williams, K. M., Day, R. O. (1994). The stereoselective disposition of the enantiomers of ibuprofen in blood, blister and synovial fluid. Br. J. Clin. Pharmacol. 38(3):221-227.
78. Sevoz, C., Benoit, E., Buronfosse, T. (2000). Thioesterification of 2-arylpropionic acids by recombinant acyl-coenzyme a synthetases (ACS1 and ACS2). Drug Metab. Dispos. 28(4):398-402.
79. Shieh, W. R., Chen, C. S. (1993). Purification and characterization of novel "2-arylpropionyl-CoA epimerases" from rat liver cytosol and mitochondria. J. Biol. Chem. 268(5):3487-3493.
80. Sivak-Sears, N. R., Schwartzbaum, J. A., Miike, R., Moghadassi, M., Wrensch, M. (2004). Case-control study of use of nonsteroidal antiinflammatory drugs and glioblastoma multiforme. Am. J. Epidemiol. 159(12):1131-1139.
81. Suzuki, H., Kawarabayasi, Y., Kondo, J., Abe, T., Nishikawa, K., Kimura, S., Hashimoto, T., Yamamoto, T. (1990). Structure and regulation of rat long chain acyl-CoA synthetase. J. Biol. Chem. 265(15):8681-8685.
82. Suzuki, H., Watanabe, M., Fujino, T., Yamamoto, T. (1995). Multiple promoters in rat acyl-CoA synthetase gene mediate differential expression of multiple transcripts with 5′-end heterogeneity. J. Biol. Chem. 270(16):9676-9682.
83. Tabrizi, A. R., Zehnbauer, B. A., Borecki, I. B., McGrath, S. D., Buchman, T. G., Freeman, B. D. (2002). The frequency and effects of cytochrome P450 (CYP) 2C9 polymorphisms in patients receiving warfarin. J. Am. Coll. Surg. 194(3):267-273.
84. Tachibana, K., Ohnishi, A. (2001). Reversed-phase liquid chromatographic separation of enantiomers on polysaccharide type chiral stationary phases. J. Chromatogr., A 906(1 -2):127-154.
85. Takahashi, H., Echizen, H. (2001). Pharmacogenetics of warfarin elimination and its clinical implications. Clin. Pharmacokinet. 40(8):587-603.
86. Tamai, I., Takanaga, H., Maeda, H., Sai, Y., Ogihara, T., Higashida, H., Tsuji, A. (1995). Participation of a proton-cotransporter, MCT1, in the intestinal transport of monocarboxylic acids. Biochem. Biophys. Res. Commun. 214(2):482-489.
87. Tan, S. C., Patel, B. K., Jackson, S. H., Swift, C. G., Hutt, A. J. (2002). Stereoselectivity of ibuprofen metabolism and pharmacokinetics following the administration of the racemate to healthy volunteers. Xenobiotica 32(8):683-697.
88. Tang, W. (2003). The metabolism of diclofenac - enzymology and toxicology perspectives. Curr. Drug Metab. 4(4):319-329.
89. Teng, X. W., Wang, S. W., Davies, N. M. (2003a). Stereospecific high-performance liquid chromatographic analysis of ibuprofen in rat serum. J. Chromatogr., B. Analy. Technol. Biomed. Life Sci. 796(2):225-231.
90. Teng, X. W., Wang, S. W., Davies, N. M. (2003b). Stereospecific high-performance liquid chromatographic analysis of flurbiprofen: application to pharmacokinetic studies. J. Pharm. Biomed. Anal. 33(1):95-100.
91. Thomason, M. J., Rhys-Williams, W., Lloyd, A. W., Hanlon, G. W. (1998). The stereo inversion of 2-arylpropionic acid non-steroidal anti-inflammatory drugs and structurally related compounds by Verticillium lecanii. J. Appl. Microbiol. 85(1):155-163.
92. Tracy, T. S., Wirthwein, D. P., Hall, S. D. (1993). Metabolic inversion of (R)-ibuprofen. Formation of ibuprofenyl-coenzyme A. Drug Metab. Dispos. 21(1):114-120.
93. Tracy, T. S., Rosenbluth, B. W., Wrighton, S. A., Gonzalez, F. J., Korzekwa, K. R. (1995). Role of cytochrome P450 2C9 and an allelic variant in the 4′-hydroxylation of (R)-and (S)-flurbiprofen. Biochem. Pharmacol. 49(9):1269-1275.
94. Vianna-Jorge, R., Perini, J. A., Rondinelli, E., Suarez-Kurtz, G. (2004). CYP2C9 genotypes and the pharmacokinetics of tenoxicam in Brazilians. Clin. Pharmacol. Ther. 76(1):18-26.
95. Waku, K. (1992). Origins and fates of fatty acyl-CoA esters. Biochim. Biophys. Acta 1124(2):102-111.
96. Wechter, W. J. (1994). Drug chirality: on the mechanism of R-aryl propionic acid classs NSAIDs. Epimerization in humans and the clinical implications for the use of racemates. J. Clin. Pharmacol. 34:1036-1042.
97. Wechter, W. J., Loughhead, D. G., Reischer, R. J., Van Giessen, G. J., Kaiser, D. G. (1974a). Enzymatic inversion at saturated carbon: Nature and mechanism of the inversion of R(-)p-isobutyl hydratropic acid. Biochem. Biophys. Res. Commun. 61(3):833-837.
98. Wechter, W. J., Loughhead, D. G., Reischer, R. J., Van Giessen, G. J., Kaiser, D. G. (1974b). The stereochemistry of the metabolism of (±)p-iso-butyl hydratropic acid, a non-steroidal anti-inflammatory (NSAI) agent. Natl. Med. Chem. Symp. 14:91-98.
99. Xie, H. G., Prasad, H. C., Kim, R. B., Stein, C. M. (2002). CYP2C9 allelic variants: ethnic distribution and functional significance. Adv. Drug Deliv. Rev. 54(10):1257-1270.
100. Yamazaki, H., Inoue, K., Chiba, K., Ozawa, N., Kawai, T., Suzuki, Y., Goldstein, J. A., Guengerich, F. P., Shimada, T. (1998). Comparative studies on the catalytic roles of cytochrome P4502C9 and its Cys-and Leu-variants in the oxidation of warfarin, flurbiprofen, and diclofenac by human liver microsomes. Biochem. Pharmacol. 56:243-251.
101. Yu, H. C. M., Chan, T. Y. K., Critchley, J. A. J. H., Woo, K. S. (1996). Factors determining the maintenance dose of warfarin in Chinese patients. Q. J. Med. 89:127-135.
102. Zhivkova, Z. D., Russeva, V. N. (1998). Stereoselective binding of ketoprofen enantiomers to human serum albumin studied by high-performance liquid affinity chromatography, especially at high concentration. J. Chromatogr., B, Biomed. Sci. Appl. 714(2):277-283.