Abstract
The application of pharmacometrics to knowledge acquisition adds value to the drug development process because it enables the translation of information about drug action and interaction with the disease process into knowledge by enabling quantitative descriptions of drug actions, and the leveraging of this knowledge across different stages of drug development. This chapter describes a pharmacometrics based strategy of evolving a drug candidate from the nonclinical phase of drug development to the early phase of clinical drug development using an anti-inflammatory drug candidate as an example. Modeling was used to extract knowledge from nonclinical data and used to simulate a first time-in-human study. The results of the simulation study formed the basis for recommending a range of doses for a single dose escalation study, which were later compared with the results of the simulation study to determine the usefulness of the approach.
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Adams CP, Brantner VV (2010) Spending on new drug development. Health Econ 19:130–141
Box GEP (1979) Robustness in the strategy of scientific model building. In: Laurer RL, Wilkinson GN (eds). Academic Press, New York, pp 275–291
Chu H-M, Zha J, Roy A, Ette EL (2007) Designs for first time-in-human studies in non-oncology indications. In: Ette EI, Williams PJ (eds) Pharmacometrics: the science of quantitative pharmacology. Wiley, Hoboken, NJ, pp 761–780
Chu H-M, Zha J, Roy A, Ette EI (2008) Determination of the efficiency of first time-in-man studies in healthy volunteers. Clin Res Regul Affairs 25:157–172
Bhattaram VA, Bonapace C, Chilukuri DM, Duan JZ, Garnett C, Gobburu JVS, Jang SH, Kenna L, Lesko LJ, Madabushi R, Men Y, Powell JR, Qiu W, Ramchandani RP, Tornoe CW, Wang Y, Zheng JJ (2007) Impact of pharmacometrics review on new drug approval and labeling decisions-a survey of 31 new drug applications submitted between 2005 and 2006. Clin Pharmacol Ther 81:213–221
Box GEP (1979) Robustness in the strategy of scientific model building. In: Laurer RL, Wilkinson GN (eds) Academic press, Newyork, pp 275–291
Bugg CE, Carson WM, Montgomery JA (1993) Drugs by design. Sci Am 269:92–98
Clemento A (1999) New and integrated approaches to successful accelerated drug development. Drug Info J 33:699–710
Cosson VF, Fuseau E (1997) Mixed effect modeling of sumatriptan pharmacokinetics during drug development. I: Interspecies allometric scaling. J Pharmacokinet Biopharm 25:149–167
Department of Health and Human Services (2004) Challenge and opportunity on the critical path to new products. US Food and Drug Administration, Rockville, MD
Derendorf H, Lesko LJ, Chaikin P, Colburn WA, Lee P, Miller R, Powell R, Rhodes G, Stanski D, Venitz J (2000) Pharmacokinetic/pharmacodynamic modeling in drug research and development. J Clin Pharmacol 40:1399–1418
DiMasi JA (2001) Risks in new drug development: approval success rates for investigational drugs. Clin Pharmacol Ther 69:297–307
DiMasi JA, Hansen RW, Grabowski HG (2003) The price of innovation: new estimates of drug development costs. J Health Econ 22:151–185
Ette EI, Williams PJ, Sun H, Fadiran EO, Ajayi FO, Onyiah LC (2001) The process of knowledge discovery from large pharmacokinetic data sets. J Clin Pharmacol 41:25–34
Ette EI, Chu H-M, Godfrey CJ (2004) Data supplementation: a pharmacokinetic/pharmacodynamic knowledge creation approach for characterizing an unexplored region of the response surface. Pharm Res 22:523–531
Kleinberg MI, Wanke LA (1995) New approaches and technologies in drug design and discovery. Am J Health Syst Pharm 52(1323–1336):1341–1343
Martin-Jimenez T, Riviere JE (2002) Mixed-effects modeling of the interspecies pharmacokinetic scaling of oxytetracycline.J Pharm Sci 91:331–341
Peck CC (1997) Drug development: improving the process. Food Drug Law J 52:163–167
Sheiner LB (1997) The intellectual health of clinical drug evaluation. Clin Pharmacol Ther 50:4–9
US Food and Drug Administration (2010) Critical path initiative. http://www.fda.gov/ScienceResearch/SpecialTopics/Critical PathInitiative/default.htm. Accessed 26 May 2010
Williams PJ, Desai A, Ette EI (2003) The role of pharmacometrics in Cardiovascular drug development. In: Pugsley MK (ed) Cardiac Drug Development Guide. Humana, Totowa, NJ, pp 365–387
Zial MR, Beer B (1990) Making business sense of science with rational drug design. Pharm Exec 10: 40, 42, 44, 46
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Ette, E.I., Godfrey, C.J. (2011). Leveraging Pharmacometrics in Early Phase Anti-inflamatory Drug Development. In: Kimko, H., Peck, C. (eds) Clinical Trial Simulations. AAPS Advances in the Pharmaceutical Sciences Series, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7415-0_8
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DOI: https://doi.org/10.1007/978-1-4419-7415-0_8
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