Stereochemistry in the drug development process: Role of chirality as a determinant of drug action, metabolism, and toxicity

Chemical Analysis

Volumn 142, Issue , 1997, Pages 21-43

  Baillie, Thomas A ^a   Schultz, Kathleen M ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0347171895     PISSN: 00692883     EISSN: None     Source Type: Book Series    
DOI: None     Document Type: Article

References (71)

1. Adams, S. S., Cliffe, E. E., Lessel, B., and Nicholson, J. S. (1967). Some biological properties of 2-(4-isobutylphenyl)-propionic acid. J. Pharm. Pharmacol., 56, 1686.
2. Adams, S. S., Bresloff, P., and Mason, C. G. (1976). Pharmacological differences between the optical isomers of ibuprofen: evidence for metabolic inversion of the (-) isomer, J. Pharm. Pharmacol., 28, 256-257.
3. Åkerman, B. and Ross, S. (1970). Stereospecificity of the enzymatic biotransformation of the enantiomers of prilocaine (Citanest). Acta Pharmacol. Toxicol., 28, 445-453.
4. Ariëns, E. J. (1984). Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology. Eur. J. Clin. Pharmacol., 26, 663-668.
5. Ariëns, E. J. (1986). Stereochemistry: A source of problems in medicinal chemistry. Med. Res. Rev., 6, 451-466.
6. Ariëns, E. J. (1993). Nonchiral, homochiral and composite chiral drugs. Trends Pharmacol. Sci., 14, 68-75.
7. Aso, Y., Yoshioka, S., Shibazaki, T., and Uchiyama, M. (1988). The kinetics of the racemization of oxazepam in aqueous solution. Chem. Pharm. Bull. (Tokyo), 36, 1834-1840.
8. Baillie, T. A. and Sheffels, P. R. (1995). Valproic acid. Chemistry and biotransformation. In Antiepileptic Drugs, 4th ed., R. H. Levy, R. H. Mattson, B. S. Meldrum (eds.), New York: Raven Press, pp. 589-604.
9. Bartels, M. J. and Smith, F. A. (1989). Stereochemical inversion of haloxyfop in the Fischer 344 rat. Drug Metab. Disp., 17, 286-291.
10. Blaschke, G., Kraft, H. P., Fickentscher K., and Köhler, F. (1979). Chromatographische racemattrennung von thalidomide und teratogene Wirkung der enantiomere. Arzneim.-Forsch. (Drug Res.), 29, 1640-1642.
11. Borgström, L., Kennedy, B.-M., Nilsson, B., and Angelin, B. (1990). Relative absorption of the two enantiomers of terbutaline after duodenal administration. Eur. J. Clin. Pharmacol., 38, 621-623.
12. Caldwell, J. (1989). St. Mary's Discussion Forum: Racemates and enantiomers: scientific and regulatory aspects. Chirality, 1, 249-250.
13. Caldwell, J., Hutt, A. J., and Fournel-Gigleux, S. (1988). The metabolic chiral inversion and dispositional enantioselectivity of the 2-arylpropionic acids and their biological consequences. Biochem. Pharmacol., 37, 105-114.
14. Carey, J. (1993). New resolutions in drug design, Chem. Brit., 29, 1053-1056.
15. Cayen, M. N. (1991). Racemic mixtures and single stereoisomers: Industrial concerns and issues in drug development. Chirality, 3, 94-98.
16. Corcoran, G. B. and Wong, B. K. (1986). Role of glutathione in prevention of acetaminophen-induced hepatotoxicity by N-acetyl-L-cysteine in vivo: Studies with N-acetyl-D-cysteine in mice. J. Pharmacol. Exp. Ther., 253, 54-61.
17. De Camp, W. H. (1989). The FDA perspective on the development of stereoisomers. Chirality, 1, 2-6.
18. Drayer, D. E. (1986). Pharmacodynamic and pharmacokinetic differences between drug enantiomers in humans: An overview. Clin. Pharmacol. Ther., 40, 125-133.
19. FDA (1992). FDA's policy statement for the development of new stereoisomeric drugs. Chirality, 4, 338-340.
20. Gibaldi, M. (1993). Stereoselective and isozyme-selective drug interactions. Chirality, 5, 407-413.
21. Gross, M., Cartwright, A., Campbell, B., Bolton, R., Holmes, K., Kirkland, K., Salmonson, T., and Robert, J.-L. (1993). Regulatory requirements for chiral drugs. Drug Inf. J., 27, 453-457.
22. Grossman, S. J., DeLuca, J. G., Zamboni, R. J., Keenan, K. P., Patrick, D. H., Herold, E. G., van Zwieten, M. J., and Zacchei, A. G. (1992). Enantioselective induction of peroxisomal proliferation in CD-1 mice by leukotriene antagonists. Toxicol. Appl. Pharmacol., 116, 217-224.
23. Hauck, R.-S. and Nau, H. (1989). Asymmetric synthesis and enantioselective teratogenicity of 2-n-propyl-4-pentenoic acid (4-en-VPA), an active metabolite of the anticonvulsant drug, valproic acid. Toxicol. Lett., 49, 41-48.
24. Hauck, R.-S., Wegner, C., Blumtritt, P., Fuhrhop, J.-H., and Nau, H. (1990). Asymmetric synthesis and teratogenic activity of (R)- and (S)-2-ethylhexanoic acid, a metabolite of the plasticizer di-(2-ethylhexyl)phthalate. Life Sci., 46, 513-518.
25. Hofmann, C. A. and Colca, J. R. (1992). New oral thiazolidinedione antidiabetic agents as insulin sensitizers. Diab. Care, 15, 1075-1078.
26. Holmes, K. D., Baum, R. G., Brenner, G. S., Eaton, C. R., Gross, M., Grundfest, C. C., Margerison, R. B., Morton, D. R., Murphy, P. J., Palling, D., Repic, O., Simon, R., and Stoll, R. E. (1990). Comments on enantiomerism in the drug development process. Pharmaceut. Technol., 14, 46-52.
27. Hutt, A. J. (1991). Drug chirality: Impact on pharmaceutical regulation. Chirality, 3, 161-164.
28. Hutt, A. J. and Caldwell, J. (1983). The metabolic chiral inversion of 2-arylpropionic acids - a novel route with pharmacological consequences. J. Pharm. Pharmacol., 35, 693-704.
29. Hutt, A. J. and Caldwell, J. (1984). The importance of stereochemistry in the clinical pharmacokinetics of the 2-arylpropionic acid non-steroidal anti-inflammatory drugs. Clin. Pharmacokinet., 9, 371-373.
30. Kashiyama, E., Todaka, T., Odomi, M., Tanokura, Y., Johnson, D. B., Yokoi, T., Kamataki, T., and Shimizu, T. (1994). Stereoselective pharmacokinetics and interconversions of flosequinan enantiomers containing chiral sulphoxide in rat. Xenobiotica, 24, 369-377.
31. Kassahun, K., Jochheim, C., and Baillie, T. A. (1994). Effect of carbamate thioester derivatives of methyl- and 2-chloroethyl isocyanate on glutathione levels and glutathione reductase activity in isolated rat hepatocytes. Biochem. Pharmacol., 48, 587-594.
32. Knadler, M. P. and Hall, S. D. (1990). Stereoselective arylpropionyl-CoA thioester formation in vitro. Chirality, 2, 67-73.
33. Knights, K. M., Talbot, U. M., and Baillie, T. A. (1992). Evidence of multiple forms of rat liver microsomal coenzyme a ligase catalysing the formation of 2-arylpropionyl-coenzyme a thioesters. Biochem. Pharmacol., 44, 2415-2417.
34. Knoche, B. and Blaschke, G. (1994). Stereoselectivity of the in vitro metabolism of thalidomide. Chirality, 6, 221-224.
35. Lee, E. J. D. and Williams, K. M. (1990). Chirality. Clinical pharmacokinetic and pharmacodynamic considerations. Clin. Pharmacokinet., 18, 339-345.
36. Levy, R. H. and Boddy, A. V. (1991). Stereoselectivity in pharmacokinetics: A general theory. Pharmaceut. Res., 8, 551-556.
37. 2 as a function of pH and temperature in aqueous solution. J. Am. Chem. Soc., 100, 1891-1895.
38. Nicholson, J. S. (1982). Ibuprofen. In Chronicles of Drug Discovery, Vol. 1, J. S. Bindra, and D. Lednicer (eds.), New York: Wiley, pp. 149-172.
39. Pepper, C., Smith, H. J., Barrell, K. J., Nicholls, P. J., and Hewlins, M. J. E. (1994). Racemization of drug enantiomers by benzylic proton abstraction at physiological pH. Chirality, 6, 400-404.
40. Pfeiffer, C. C. (1956). Optical isomerism and pharmacological action, a generalization. Science, 124, 29-31.
41. Polhuijs, M., Tergau, A. C., and Mulder, G. J. (1992). Chiral inversion and stereoselective glutathione conjugation of the four 2-bromo-3-methylvaleric acid stereoisomers in the rat in vivo and in vitro. J. Pharmacol. Exp. Ther., 260, 1349-1354.
42. Porubek, D. J., Barnes, H., Meier, G. P., Theodore, L. J., and Baillie, T. A. (1989). Enantiotopic differentiation during the biotransformation of valproic acid to the hepatotoxic olefin 2-n-propyl-4-pentenoic acid. Chem. Res. Toxicol., 2, 35-40.
43. Porubek, D. J., Sanins, S. M., Stephens, J. R., Grillo, M. P., Kaiser, D. G., Halstead, G. W., Adams, W. J., and Baillie, T. A. (1991). Metabolic chiral inversion of flurbiprofen-CoA in vitro. Biochem. Pharmacol., 42, R1-R4.
44. Rauws, A. G. and Groen, K. (1994). Current regulatory (draft) guidance on chiral medicinal products: Canada, EEC, Japan, United States. Chirality, 6, 72-75.
45. Sanins, S. M., Adams, W. J., Kaiser, D. G., Halstead, G. W., Hosley, J., Barnes, H., and Baillie, T. A. (1991). Mechanistic studies on the metabolic chiral inversion of R-ibuprofen in the rat. Drug Metab. Dispos., 19, 405-410.
46. Särnstrand, B., Tunek, A., Sjödin, K., and Hallberg, A. (1995). Effects of N-acetylcysteine stereoisomers on oxygen-induced lung injury in rats. Chem.-Biol. Inter., 94, 157-164.
47. Schmahl, H.-J., Heger, W., and Nau, H. (1989). The enantiomers of the teratogenic thalidomide analogue EM12. Toxicol. Lett., 45, 23-33.
48. Schmahl, H.-J., Nau, H., and Neubert, D. (1988). The enantiomers of the teratogenic thalidomide analogue EM12: 1. Chiral inversion and plasma pharmacokinetics in the marmoset monkey. Arch. Toxicol., 62, 200-204.
49. Shen, D. D., Levy, R. H., Savitch, J. L., Boddy, A. V., Lepage, F., and Tombret, F. (1992). Comparative anticonvulsant potency and pharmacokinetics of (+)- and (-)-enantiomers of stiripentol. Epilepsy Res., 12, 29-36.
50. Shieh, W.-R. and Chen, C.-S. (1993). Purification and characterization of novel "2-arylpropionyl-CoA epimerases" from rat liver cytosol and mitochondria. J. Biol. Chem., 268, 3487-3493.
51. Shindo, H. and Caldwell, J. (1991). Regulatory aspects of the development of chiral drugs in Japan: A status report. Chirality, 3, 91-93.
52. Shirley, M. A., Hu, P., and Baillie, T. A. (1993). Stereochemical studies on the β-ox7idation of valproic acid in isolated rat hepatocytes. Drug Metab. Disp., 21, 580-586.
53. Shirley, M. A., Guan, X., Kaiser, D. G., Halstead, G. W., and Baillie, T. A. (1994). Taurine conjugation of ibuprofen in humans and in rat liver in vitro. Relationship to metabolic chiral inversion. J. Pharmacol. Exp. Ther., 269, 1166-1175.
54. Sohda, T., Mizuno, K., and Kawamatsu, Y. (1984). Studies on antidiabetic agents. VI. Asymmetric transformation of (±)-5-[4-(1-methylcyclohexylmethoxy)benzyl]-2,4-thiazolidinedione (ciglitazone) with optically active 1-phenylethylamines. Chem. Pharm. Bull. (Tokyo), 32, 4460-4465.
55. Stinson, S. C. (1992). Chiral drugs. Chem. Brit, 28, 46-79.
56. Stinson, S. C. (1994). Chiral drugs. New single-isomer products on the chiral drug market create demand for enantiomeric intermediates and enantioseletive technologies. Chem. Eng. News, 72 (38), 38-72.
57. Tang, C., Lepage, F., and Baillie, T. A. (1995). Unpublished results.
58. Tang, C., Zhang, K., Lepage, R. Levy, R. H., and Baillie, T. A. (1994). Metabolic chiral inversion of stiripentol in the rat. II. Influence of route of administration. Drug Metab. Disp., 22, 554-560.
59. Testa, B. (1989). Mechanisms of chiral recognition in xenobiotic metabolism and drug-receptor interactions. Chirality, 1, 7-9.
60. Testa, B. and Trager, W. F. (1990). Racemates versus enantiomers in drug development: Dogmatism or pragmatism? Chirality, 2, 129-133.
61. Testa, B., Carrupt, P.-A., and Gal, J. (1993). The so-called "interconversion" of stereoisomeric drugs: An attempt at clarification, Chirality, 5, 105-111.
62. Vermeulen, N. P. E. and te Koppele, J. M. (1993). Stereoselective biotransformation. Toxicological consequences and implications. In Drug Stereochemistry. Analytical Methods and Pharmacology, 2nd ed. I. W. Wainer (ed.), New York: Marcel Dekker, pp. 245-280.
63. Wainer, I. W. (ed.) (1993). Drug Stereochemistry. Analytical Methods and Pharmacology, 2nd. ed. New York: Marcel Dekker.
64. Williams, K. M. (1990). Enantiomers in arthritic disorders. Pharmacol. Ther., 46, 273-295.
65. Williams, K. M. (1991). Molecular asymmetry and its pharmacological consequences. Adv. Pharmacol., 22, 57-135.
66. Wilson, K. and Walker, J. (eds.) (1991). Chirality and its importance in drug development. Biochem. Soc. Trans., 19, 443-475.
67. Yang, S. K. (1994). Acid-catalyzed stereoselective heteronucleophilic substitution and racemization of 3-O-methyloxazepam and 3-O-ethyloxazepam. Chirality, 6, 175-184.
68. Yang, S. K. and Bao, Z. (1994). Base-catalyzed racemization of 3-O-acyloxazepam. Chirality, 6, 321-328.
69. Yang, S. K. and Lu, X.-L. (1989). Racemization kinetics of enantiomeric oxazepams and stereoselective hydrolysis of enantiomeric oxazepam 3-acetates in rat liver microsomes and brain homogenate. J. Pharmaceut. Sci., 78, 789-795.
70. Yang, S. K. and Lu, X.-L. (1992). Resolution and stability of oxazepam enantiomers. Chirality, 4, 443-446.
71. Zhang, K., Tang, C., Rashed, M., Cui, D., Tombret, F., Botte, H., Lepage, F., Levy, R. H., and Baillie, T. A. (1994). Metabolic chiral inversion of stiripentol in the rat. I. Mechanistic studies. Drug Metab. Disp., 22, 544-553.