YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

The Role and Application of Biomarkers and Surrogate Endpoints for New Drug Development : Focused on Diabetes Mellitus and Osteoporosis

당뇨병 및 골다공증 치료제의 효율적인 신약개발을 위한 생체표지자 및 대리 결과 변수의 역할 및 활용

  • Seong, Soo-Hyeon (College of Pharmacy, Chungnam National University) ;
  • Yun, Hwi-Yeol (College of Pharmacy, Chungnam National University) ;
  • Baek, In-Hwan (College of Pharmacy, Chungnam National University) ;
  • Kang, Won-Ku (College of Pharmacy, Catholic University of Daegu) ;
  • Chang, Jung-Yun (Gastrointestinal, Urinary and Metabolic Drug Team, Korea Food and Drug Administration) ;
  • Seo, Kyung-Won (Gastrointestinal, Urinary and Metabolic Drug Team, Korea Food and Drug Administration) ;
  • Kwon, Kwang-Il (College of Pharmacy, Chungnam National University)
  • 성수현 (충남대학교 약학대학 임상약학 연구실) ;
  • 윤휘열 (충남대학교 약학대학 임상약학 연구실) ;
  • 백인환 (충남대학교 약학대학 임상약학 연구실) ;
  • 강원구 (대구 가톨릭대학교 약학대학 임상약학 연구실) ;
  • 장정윤 (식품의약품안전청 기관계용의약품팀) ;
  • 서경원 (식품의약품안전청 기관계용의약품팀) ;
  • 권광일 (충남대학교 약학대학 임상약학 연구실)
  • Published : 2008.10.31
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Abstract

Recently, the FDA (Food and Drug Administration) of the United States and many advanced countries remark biomarkers and surrogate endpoints as a critical path tool on model based drug development. Economic, technical and social profit on model based drug development like a reduction of the length of research and development have been achieved. Therefore we summarize previous studies about biomarkers and surrogate endpoints and suggest a development direction of therapeutic agents. In diabetes mellitus (DM) and osteoporosis, there are remarkable increases in number of patients and most of patients take medicine during their whole lifetime. For this reason, many patients with DM and osteoporosis have a tolerance on their medicine. We expect that research and development on biomarkers and surrogate endpoints will contribute to new drug development on DM and osteoporosis. Biomarkers for DM are blood levels of glucose, insulin, ${HbA}_{1c}$, CRP, alpha-glucosidase, adiponectin and DPP-4. Among these, validated surrogate endpoints for DM are blood levels of glucose, insulin and ${HbA}_{1c}$ Biomarkers for osteoporosis are BMD, BMC, trabecular volume, ICTP, DPD, osteocalcin, the activity of osteoclast and production of osteoblast. The validated surrogate endpoints for osteoporosis are BMD only. This review summarizes all suggested biomarkers and surrogate endpoints in DM and osteoporosis. The biomarkers are classified by drugs, and the method of validation for surrogate endpoints is suggested. This information would contribute to suggest a direction of DM and osteoporosis therapeutic agent development.

Keywords

References

  1. Woosley, R. L. and Cossman, J. : Drug development and the FDA's critical path initiative. Clin. Pharmacol. Ther. 81(1), 129 (2007) https://doi.org/10.1038/sj.clpt.6100014
  2. Revision of Committee : Challenge and Opportunity on the critical path to new medical product. FDA (2004)
  3. Wagner, J. A. : Overview of biomarkers and surrogate endpoints in drug development. Dis. Markers 18, 41 (2002) https://doi.org/10.1155/2002/929274
  4. Biomarkers Definition working group (BDWG) : Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin. Pharmacol. Ther. 69(3), 89 (2001) https://doi.org/10.1067/mcp.2001.113989
  5. De Gruttola, V. G., Clax, P., DeMets, D. L., Downing, G. J., Ellenberg, S. S., Friedman, L., Gail, M. H., Prentice, R., Wittes, J. and Zeger, S. L. : Considerations in the Evaluation of Surrogate endpoints in clinical trials: Summary of national institutes of health workshop. Control. Clin. Trials. 22, 485 (2001)
  6. Revision of Committee : Critical path opportunites reports. FDA (2006) : on-line service
  7. Stanski, D. R. : Model-based drug development : A critical path opportunity. FDA (2006)
  8. Revision of Committee : Post-genomic biomarker. Bioview 12(3), (2004)
  9. Bruno, R. : Impact of PK/PD modeling and simulation in drug development. 13th NA ISSX/20th JSSX meeting in Maui Hawaii. (2005)
  10. Rosenstock, J., Brazg, R., Andryuk, P. J., Lu, K. and Stein, P. : Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin. Ther. 28(10), 1556 (2006) https://doi.org/10.1016/j.clinthera.2006.10.007
  11. Meigs, J. B., Panhuysen, C. I., Myers, R. H., Wilson, P. W. and Cupples, L. A. : A genome-wide scan for Loci linked to plasma levels of glucose and $HbA_{1c}$ in a community-based sample of caucasian pedigrees. Diabetes 51, 833 (2002) https://doi.org/10.2337/diabetes.51.3.833
  12. Meigs, J. B., O'donnell, C. J., Tofler, G. H., Benjamin, E. J., Fox, C. S., Lipinska, I., Nathan, D. M., Sullivan, L. M., D'Agostino, R. B. and Wilson, P. W. : Hemostatic markers of endothelial dysfunction and risk of incident type 2 diabetes. Diabetes 55, 530 (2006) https://doi.org/10.2337/diabetes.55.02.06.db05-1041
  13. Kanauchi, M., Kanauchi, K., Inoue, T., Kimura, K. and Saito, Y. : Surrogate markers of insulin resistence in assessing individuals with new categories "prehypertention" and "prediabetes". Clin. Chem. Lab. Med. 45(1), 35 (2007) https://doi.org/10.1515/CCLM.2007.015
  14. Gungor, N., Saad, R., Janosky, J. and Arslanian, S. : Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents. J. Pediatr. 144, 47 (2004) https://doi.org/10.1016/j.jpeds.2003.09.045
  15. Groop, L., Groop, P. H., Stenman, S., Saloranta, C., Totterman, K. J., Fyhrquist, F. and Melander, A. : Comparison of pharmacokinetics, metabolic effects and mechanisms of action of glyburide and glipizide during long-term treatment. Diabetes Care 10(6), 71 (1987) https://doi.org/10.2337/diacare.10.6.71
  16. Smirnakis, K. V., Plati, A., Wolf, M., Thadhani, R. and Ecker, J. L. : Predicting gestational diabetes: choosing the optimal early serum marker. Am. J. Obstet. Gynecol. 196(4), 410.e1-410.e7 (2007) https://doi.org/10.1016/j.ajog.2006.12.011
  17. Stepensky, D., Friedman, M., Raz, I. and Hoffman, A. : Pharmacokinetic-pharmacodynamic analysis of the glucoselowering effect of metformin in diabetic rats reveals first-pass pharmacodynamic effect. Drug Metab. Dispos. 30(8), 861 (2002) https://doi.org/10.1124/dmd.30.8.861
  18. Yale, J. F., Valiquett, T. R., Ghazzi, M. N., Owens-Grillo, J. K., Whitcomb, R. W. and Foyt, H. L. : The effect of a thiazolidinedione drug, troglitazone, on glycemia in patients with type 2 diabetes mellitus poorly controlled with sulfonylurea and metformin. A multicenter, randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 134, 737 (2001) https://doi.org/10.7326/0003-4819-134-9_Part_1-200105010-00010
  19. Fonseca, V., Rosenstock, J., Patwardhan, R. and Salzman, A. : Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial. JAMA 283(13), 1695 (2000) https://doi.org/10.1001/jama.283.13.1695
  20. Bischoff, H. : Pharmacology of alpha-glucosidase inhibition. Eur. J. Clin. Invest. 24, 3 (1994) https://doi.org/10.1111/j.1365-2362.1994.tb02249.x
  21. Bischoff, H. : The mechanism of alpha-glucosidase inhibitor in the management of diabetes. Clin. Invest. Med. 18(4), 303 (1995)
  22. Fernandez-Real, J. M., Lopez-Bermejo, A., Casamitjana, R. and Ricart, W. : Novel interactions of adiponectin with the endocrine system and inflammatory parameters. J. Clin. Endocrinol. Metab. 88, 2714 (2003) https://doi.org/10.1210/jc.2002-021583
  23. Bergman, A. J., Stevens, C., Zhou, Y., Yi, B., Laethem, M., De Smet, M., Snyder, K., Hilliard, D., Tanaka, W., Zeng, W., Tanen, M., Wang, A. Q., Chen, L., Winchell, G., Davies, M. J., Ramael, S., Wagner, J. A. and Herman, G. A. : Pharmacokinetic and pharmacodynamic properties of multiple oral dose of sitagliptin, a dipeptidyl peptidase-4 inhibitor: a double-blind, randomized, placebo-controlled study in healthy male volunteers. Clin. Ther. 28(1), 55 (2006) https://doi.org/10.1016/j.clinthera.2006.01.015
  24. Herman, G. A., Bergman, A., Liu, F., Stevens, C., Wang, A. Q., Zeng, W., Chen, L., Snyder, K., Hilliard, D., Tanen, M., Tanaka, W., Meehan, A. G., Lasseter, K., Dilzer, S., Blum, R. and Wagner, J. A. : Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J. Clin. Pharmacol. 46(8), 876 (2006) https://doi.org/10.1177/0091270006289850
  25. Herman, G. A., Stevens, C., Van Dyck, K., Bergman, A., Yi, B., De Smet, M., Snyder, K., Hilliard, D., Tanen, M., Tanaka, W., Wang, A. Q., Zeng, W., Musson, D., Winchell, G., Davies, M. J., Ramael, S., Gottesdiener, K. M. and Wagner, J. A. : Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase 4, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin. Pharmacol. Ther. 78(6), 675 (2005) https://doi.org/10.1016/j.clpt.2005.09.002
  26. Haidar, S. H., Johnson, S. B., Fossler, M. J. and Hussain, A. S. : Modeling the pharmacokinetics and pharmacodynamics of a unique oral hypoglycemic agent using neural networks. Pharm. Res. 19(1), 87 (2002) https://doi.org/10.1023/A:1013611617787
  27. Kolterman, O. G., Kim, D. D., Shen, L., Ruggles, J. A., Nielsen, L. L., Fineman, M. S. and Baron, A. D. : Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am. J. Health-Syst. Ph. 62(2), 173 (2005)
  28. Agerso, H. and Vicini, P. : Pharmacodynamics of NN2211, a novel long acting GLP-1 derivative. Eur. J. Pharm. Sci. 19(2-3), 141 (2003) https://doi.org/10.1016/S0928-0987(03)00073-3
  29. Nyholm, B., Brock, B., Orskov, L. and Schmitz, O. : Amylin receptor agonists: a novel pharmacological approach in the management of insulin-treated diabetes mellitus. Expert. Opin. Inv. Drug. 10(9), 1641 (2001) https://doi.org/10.1517/13543784.10.9.1641
  30. Ellerington, M. C., Hillard, T. C., Whitcroft, S. I., Marsh, M. S., Lees, B., Banks, L. M., Whitehead, M. I. and Stevenson, J. C. : Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis. Calcif. Tissue. Int. 59, 6 (1996) https://doi.org/10.1007/s002239900076
  31. Ofluoglu, D., Akyuz, G., Unay, O. and Kayhan, O. : The effect of calcitonin on beta-endorphin levels in postmenopausal osteoporotic patients with back pain. Clin. Rheumatol. 26, 44 (2007) https://doi.org/10.1007/s10067-006-0228-z
  32. Chesnut, C. H. 3rd., Majumdar, S., Newitt, D. C., Shields, A., Van Pelt, J., Laschansky, E., Azria, M., Kriegman, A., Olson, M., Eriksen, E. F. and Mindeholm, L. : Effects of salmon calcitonin on trabecular microarchitecture as determined by magnetic resonance imaging: Results from the QUEST study. J. Bone. Miner. Res. 20, 1548 (2005) https://doi.org/10.1359/JBMR.050411
  33. Abildgaard, N., Brixen, K., Eriksen, E. F., Kristensen, J. E., Nielsen, J. L. and Heickendorff, L. : Sequential analysis of biochemical markers of bone resorption and bone densitometry in multiple myeloma. Haematologica 89(5), 567 (2004)
  34. Lane, N. E., Haupt, D., Kimmel, D. B., Modin, G. and Kinney, J. H. : Early estrogen replacement therapy reverses the rapid loss of trabecular bone volume and prevents further deterioration of connectivity in the rat. J. Bone Miner. Res. 14, 206 (1999) https://doi.org/10.1359/jbmr.1999.14.2.206
  35. Okabe, R., Inaba, M., Nakatsuka, K., Miki, T., Naka, H., Moriguchi, A. and Nishizawa, Y. : Significance of serum CrossLaps as a predictor of changes in bone mineral density during estrogen replacement therapy; comparison with serum carboxyterminal telopeptide of type I collagen and urinary deoxypyridinoline. J. Bone Miner. Metab. 22, 127 (2004) https://doi.org/10.1007/s00774-003-0460-4
  36. Matsunaga, S., Ito, H. and Sakou, T. : The effect of vitamin K and D supplementation on ovariectomy-induced bone loss. Calcif. Tissue Int. 65, 285 (1999) https://doi.org/10.1007/s002239900700
  37. Kruse, K. and Kracht, U. : Evaluation of serum osteocalcin as an index of altered bone metabolism. Eur. J. Pediatr. 145, 27 (1986) https://doi.org/10.1007/BF00441848
  38. Anderson, J., Bannister, D. W., Parsons, V. and Tomlinson, R. W. : Total urinary hydroxyproline excretion in osteomalacia. Calcif. Tissue Res. 1, 183 (1967) https://doi.org/10.1007/BF02008089
  39. Heikinheimo, R. J., Inkovaara, J. A., Harju, E. J., Haavisto, M. V., Kaarela, R. H., Kataja, J. M., Kokko, A. M., Kolho, L. A. and Rajala, S. A. : Annual injection of vitamin D and fractures of aged bones. Calcif. Tissue Int. 51, 105 (1992) https://doi.org/10.1007/BF00298497
  40. Sorva, A., Risteli, J., Risteli, L., Valimaki, M. and Tilvis, R. : Effects of vitamin D and calcium on markers of bone metabolism in geriatric patients with low serum 25- hydroxyvitamin D levels. Calcif. Tissue Int. 49(suppl), 88 (1991) https://doi.org/10.1007/BF02555103
  41. Adachi, J. D., Saag, K. G., Delmas, P. D., Liberman, U. A., Emkey, R. D., Seeman, E., Lane, N. E., Kaufman, J. M., Poubelle, P. E., Hawkins, F., Correa-Rotter, R., Menkes, C. J., Rodriguez-Portales, J. A., Schnitzer, T. J., Block, J. A., Wing, J., McIlwain, H. H., Westhovens, R., Brown, J., Melo-Gomes, J. A., Gruber, B. L., Yanover, M. J., Leite, M. O., Siminoski, K. G., Nevitt, M. C., Sharp, J. T., Malice, M. P., Dumortier, T., Czachur, M., Carofano, W. and Daifotis, A. : Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids. Arthritis Rheum. 44, 202 (2001) https://doi.org/10.1002/1529-0131(200101)44:1<202::AID-ANR27>3.0.CO;2-W
  42. Shah, H. D. : Novel agents in osteoporosis. Indian J. Pharmacol. 36, 48 (2004)
  43. Edwards, C. J., Russell, R. G. and Spector, T. D. : Statins and Bone: Myth or Reality? Calcif. Tissue Int. 69, 63 (2001) https://doi.org/10.1007/s00223-001-2017-7
  44. Colburn, W. A. : Biomarkers in drug discovery and development: From target identification through drug marketing. J. Clin. Pharmacol. 43, 329 (2003) https://doi.org/10.1177/0091270003252480
  45. Lee, J. W., Devanarayan, V., Barrett, Y. C., Weiner, R., Allinson, J., Fountain, S., Keller, S., Weinryb, I., Green, M., Duan, L., Rogers, J. A., Millham, R., O'Brien, P. J., Sailstad, J., Khan, M., Ray, C. and Wagner, J. A. : Fit-for-purpose method development and validation for successful biomarker measurement. Pharm. Res. 23(2), 312 (2006) https://doi.org/10.1007/s11095-005-9045-3
  46. Lee, J. W., Smith, W. C., Nordblom, G. D. and Bowsher, R. R. : Validation of assays for the bioanalysis of novel biomarkers: Practical recommendations for clinical investigation of new drug entities. Biomarkers in Clinical Drug Development 132, 119 (2003)
  47. Colburn, W. A. : Optimiziing the use of biomarkers, surrogate endpoints, and clinical endpoints for more efficient drug development. J. Clin. Pharmacol. 40, 1419 (2000)
  48. Lesko, L. J. and Atkinson, A. J. : Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: criteria, validation, strategies. Annu. Rev. Pharmacol. 41, 347 (2001) https://doi.org/10.1146/annurev.pharmtox.41.1.347
  49. Wagner, J. A. : Biomarker validation and qualification: Fitness for use. Biomarker World Congress (2007)
  50. Rolan, P. : The contribution of clinical pharmacology surrogates and models to drug developoment-a critical appraisal. Brit. J. Clin. Pharmaco. 44, 219 (1997) https://doi.org/10.1046/j.1365-2125.1997.t01-1-00583.x
  51. Herman, G. A., Bergman, A., Stevens, C., Kotey, P., Yi, B., Zhao, P., Dietrich, B., Golor, G., Schrodter, A., Keymeulen, B., Lasseter, K. C., Kipnes, M. S., Snyder, K., Hilliard, D., Tanen, M., Cilissen, C., De Smet, M., de Lepeleire, I., Van Dyck, K., Wang, A. Q., Zeng, W., Davies, M. J., Tanaka, W., Holst, J. J., Deacon, C. F., Gottesdiener, K. M. and Wagner, J. A. : Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. J. Clin. Endocr. Metab. 91(11), 4612 (2006) https://doi.org/10.1210/jc.2006-1009
  52. Rosen, C. J. and Tenenhouse, A. : Biochemical markers of bone turnover. A look at laboratory tests that reflect bone status. Postgrad. Med. 104(4), p. 101-2, p. 107-10, p. 113-4 (1998)
  53. Waugh, J., Keating, G. M., Plosker, G. L., Easthope, S. and Robinson, D. M. : Pioglitazone: a review of its use in type 2 diabetes mellitus. Drugs 66(1), 85 (2006) https://doi.org/10.2165/00003495-200666010-00005
  54. Lachin, J. M., Genuth, S., Nathan, D. M. and Rutledge, B. N. : The hemoglobin glycation index is not an independent predictor of the risk of microvascular complications in the diabetes control and complications trial. Diabetes 56, 1913 (2007) https://doi.org/10.2337/db07-0028
  55. Dailey, G. : Assessing glycemic control with self-monitoring of blood glucose and hemoglobin A(1c) measurements. Mayo. Clin. Proc. 82(2), 229 (2007)
  56. Shultis, W. A., Leary, S. D., Ness, A. R., Scott, J., Martin, R. M., Whincup, P. H. and Smith, G. D. : Haemoglobin A1c is not a surrogate for glucose and insulin measures for investigating the early life and childhood determinants of insulin resistance and Type 2 diabetes in healthy children. An analysis from the Avon Longitudinal Study of Parents and Children (ALSPAC). Diabet. Med. 23(12), 1357 (2006) https://doi.org/10.1111/j.1464-5491.2006.01990.x
  57. Jorgensen, L. G. M., Petersen, P. H. and Brandslund, I. : Clinical outcome estimates based on treatment target limits of laboratory tests: proposal for a plot visualizing effects and differences of medical target setting exemplified by glycemic control in diabetes. Clin. Chem. Lab. Med. 44(3), 327 (2006) https://doi.org/10.1515/CCLM.2006.057
  58. Basu, S., Larsson, A., Vessby, J., Vessby, B. and Berne, C. : Type 1 diabetes is associated with increased cyclooxygenaseand cytokine-mediated inflammation. Diabetes Care 28, 1371 (2005) https://doi.org/10.2337/diacare.28.6.1371
  59. Hu, F. B., Meigs, J. B., Li, T. Y., Rifai, N. and Manson, J. E. : Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 53, 693 (2004) https://doi.org/10.2337/diabetes.53.3.693
  60. Jonsson, A., Chan, J. C., Rydberg, T., Vaaler, S., Hallengren, B., Cockram, C. S., Critchley, J. A. and Melander, A. : Pharmacodynamics and pharmacokinetics of intravenous glibenclamide in Caucasian and Chinese patients with type-2 diabetes. Eur. J. Clin. Pharmacol. 55(10), 721 (2000) https://doi.org/10.1007/s002280050004
  61. de Winter, W., DeJongh, J., Post, T., Ploeger, B., Urquhart, R., Moules, I., Eckland, D. and Danhof, M. : A mechanism-based disease progression model for comparison of long-term effects of pioglitazone, metformin and gliclazide on disease processes underlying Type 2 Diabetes Mellitus. J. Pharmacokinet. Phar. 33(3), 313 (2006) https://doi.org/10.1007/s10928-006-9008-2
  62. Gangji, A. S., Cukierman, T., Gerstein, H. C., Goldsmith, C. H. and Clase, C. M. : A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin. Diabetes Care 30(2), 389 (2007) https://doi.org/10.2337/dc06-1789
  63. Roberts, V. L., Stewart, J., Issa, M., Lake, B. and Melis, R. : Triple therapy with glimepiride in patients with type 2 diabetes mellitus inadequately controlled by metformin and a thiazolidinedione: results of a 30-week, randomized, double-blind, placebo-controlled, parallel-group study. Clin. Ther. 27(10), 1535 (2005) https://doi.org/10.1016/j.clinthera.2005.10.017
  64. Culy, C. R. and Jarvis, B. : Repaglinide: a review of its therapeutic use in type 2 diabetes mellitus. Drugs 61(11), 1625 (2001) https://doi.org/10.2165/00003495-200161110-00008
  65. Kradjan, W. A., Takeuchi, K. Y., Opheim, K. E. and Wood, F. C. Jr. : Pharmacokinetics and pharmacodynamics of glipizide after once daily and divided dose. Pharmacotherapy 15(4), 465 (1995)
  66. Kim, H., Yun, M. and Kwon, K. I. : Pharmacokinetic and pharmacodynamic characterization of gliclazide in healthy volunteers. Arch. Pharm. Res. 26(7), 564 (2003) https://doi.org/10.1007/BF02976882
  67. Frey, N., Laveille, C., Paraire, M., Francillard, M., Holford, N. H. and Jochemsen, R. : Population PKPD modelling of the long-term hypoglycaemic effect of gliclazide given as a once-aday modified release (MR) formulation. Brit. J. Clin. Pharmaco. 55(2), 147 (2003) https://doi.org/10.1046/j.1365-2125.2003.01751.x
  68. Chung, M. : Pharmacokinetics and pharmacodynamics of extended-release glipizide GITS compared with immediaterelease glipizide in patients with type 2 diabetes mellitus. J. Clin. Pharmacol. 42(6), 651 (2002) https://doi.org/10.1177/00970002042006007
  69. Bernaoe, M., Czech, A. and Taton, J. : Relative effectiveness of tolbutamide, chlorpropamide and gliclazide. Pol. Tyg. Lek. 47(1-2), 35 (1992)
  70. Jaber, L. A., Antal, E. J., Slaughter, R. L. and Welshman, I. R. : Comparison of pharmacokinetics and pharmacodynamics of short- and long-term glyburide therapy in NIDDM. Diabetes Care 17(11), 1300 (1994) https://doi.org/10.2337/diacare.17.11.1300
  71. Jaber, L. A., Antal, E. J. and Welshman, I. R. : Pharmacokinetics and pharmacodynamics of glyburide in young and elderly patients with non-insulin-dependent diabetes mellitus. Ann. Pharmacother. 30(5), 472 (1996) https://doi.org/10.1177/106002809603000507
  72. Yun, H. Y., Park, H. C., Kang, W. and Kwon, K. I. : Pharmacokinetic and pharmacodynamic modelling of the effects of glimepiride on insulin secretion and glucose lowering in healthy humans. J. Clin. Pharm. Ther. 31(5), 469 (2006) https://doi.org/10.1111/j.1365-2710.2006.00766.x
  73. Badian, M., Korn, A., Lehr, K. H., Malerczyk, V. and Waldhausl, W. : Pharmacokinetics and pharmacodynamics of the hydroxymtabolite of glimepiride (Amaryl) after intravenous administration. Drug Metabol. Drug Interact. 13(1), 69 (1996)
  74. von Nicolai, H., Brickl, R., Eschey, H., Greischel, A., Heinzel, G., Konig, E., Limmer, J. and Rupprecht, E. : Duration of action and pharmacokinetics of the oral antidiabetic drug gliquidone in patients with non-insulin-dependent (type 2) diabetes mellitus. Arzneimittelforschung 47(3), 247 (1997)
  75. Rydberg, T., Jonsson, A., Karlsson, M. O. and Melander, A. : Concentration-effect relations of glibenclamide and its active metabolites in man: modelling of pharmacokinetics and pharmacodynamics. Brit. J. Clin. Pharmaco. 43(4), 373 (1997) https://doi.org/10.1111/j.1365-2125.1997.00571.x
  76. Coppack, S. W., Lant, A. F., McIntosh, C. S. and Rodgers, A. V. : Pharmacokinetic and pharmacodynamic studies of glibenclamide in non-insulin dependent diabetes mellitus. Brit. J. Clin. Pharmaco. 29(6), 673 (1990) https://doi.org/10.1111/j.1365-2125.1990.tb03688.x
  77. el-Sayed, Y. M., Suleiman, M. S., Hasan, M. M., Abdel-Hamid, M. E., Najib, N. M., Sallam, E. S. and Shubair, M. S. : Comparison of the pharmacokinetics and pharmacodynamics of two commercial products containing glibenclamide. Int. J. Clin. Pharmacol. Ther. Toxicol. 27(11), 551 (1989)
  78. Lee, P. E., Gill, S. S., Freedman, M., Bronskill, S. E., Hillmer, M. P. and Rochon, P. A. : Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review. Brit. Med. J. 329, 75 (2004) https://doi.org/10.1136/bmj.38125.465579.55
  79. Wagner, J. A. : Early clinical development of pharmaceuticals for type 2 diabetes mellitus: from preclinical models to human investigation. J. Clin. Endocrinol. Metab. 87(12), 5362 (2002) https://doi.org/10.1210/jc.2002-020910
  80. Wagner, J. A. : Overview of biomarkers and surrogate endpoints in drug development. Dis. Markers 18, 41 (2002) https://doi.org/10.1155/2002/929274
  81. Schwartz, S., Raskin, P., Fonseca, V. and Graveline, J. F. : Effect of troglitazone in insulin-treated patients with type 2 diabetes mellitus. Troglitazone and exogenous insulin study group. New Engl. J. Med. 338(13), 861 (1998) https://doi.org/10.1056/NEJM199803263381302