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Anticancer Clinical Pharmacology Overview

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Handbook of Anticancer Pharmacokinetics and Pharmacodynamics

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

This chapter is an overview of the principles of clinical pharmacology with a focus on oncology therapeutics. It covers the basic pharmacologic principles of pharmacokinetics and pharmacodynamics which underpin the individualization of a patient’s drug therapy and focuses on the utilization of these principles in anticancer drug therapy prescribing while addressing some of the most recent advances in the field. A unique aspect of this chapter is the intention to bridge the gap between clinical pharmacologists and subspecialty oncologists. This chapter showcases the rationale as to why the discipline of clinical pharmacology plays an increasingly significant role in clinical therapeutics (prescribing) in all specialties where drugs are used to treat disease.

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References

  1. Ross EM, Kenakin TP (2001) Pharmacodynamics: mechanisms of drug action and the relationship between drug concentration and effect. In: Hardman JG, Limbird LE (eds) Goodman & Gilman’s the pharmacological basis of therapeutics, 10th edn. McGraw-Hill, New York, NY, pp 31–43

    Google Scholar 

  2. Nies AS (2001) Principles of therapeutics. In: Hardman JG, Limbird LE (eds) Goodman & Gilman’s the pharmacological basis of therapeutics, 10th edn. McGraw-Hill, New York, NY, pp 45–66

    Google Scholar 

  3. Lowe ES, Balis FM (2007) Dose-effect and concentration-effect analysis. In: Atkinson AJ, Abernethy DR, Daniels CE, Dedrick RL, Markey SP (eds) Principles of clinical pharmacology. Academic, Boston, pp 289–299

    Chapter  Google Scholar 

  4. Ritter JM, Lewis LD, Mant TGK, Ferro A (2008) A textbook of clinical pharmacology, 5th edn. Arnold, London, pp 6–85

    Google Scholar 

  5. Atkinson AJ (2001) Kinetic analysis of pharmacologic effect. In: Atkinson AJ, Daniels CE, Dedrick RL, Grudzinskas CV, Markey SP (eds) Principles of clinical pharmacology. Academic, Boston, pp 245–252

    Google Scholar 

  6. Nierenberg DW, Melmon KL (2000) Introduction to clinical pharmacology and rational therapeutics. In: Carruthers GS, Hoffman BB, Melmon KL, Nierenberg DW (eds) Melmon and Morrelli’s clinical pharmacology, 4th edn. McGraw-Hill, New York, pp 3–62

    Google Scholar 

  7. Kenakin TP, Bond RA, Bonner TI (1992) Definition of pharmacological receptors. Pharmacol Rev 44:351–362

    CAS  PubMed  Google Scholar 

  8. Christopoulos A, Kenakin T (2002) G Protein-coupled receptor allosterism and complexing. Pharmacol Rev 54:323–374

    Article  CAS  PubMed  Google Scholar 

  9. Capdeville R, Buchdunger E, Zimmermann J, Matter A (2002) Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat Rev Drug Discov 1:493–502

    Article  CAS  PubMed  Google Scholar 

  10. Druker BJ, Talpaz M, Resta DJ et al (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344:1031–1037

    Article  CAS  PubMed  Google Scholar 

  11. Van Oosterom AT, Judson I, Verweij J et al (2001) Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet 358:1421–1423

    Article  PubMed  Google Scholar 

  12. Smith PF, DiCenzo R, Morse GD (2001) Clinical pharmacokinetics of non-nucleoside reverse transcriptase inhibitors. Clin Pharmacokinet 40:893–905

    Article  CAS  PubMed  Google Scholar 

  13. Macgregor JI, Jordan VC (1998) Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev 50:151–196

    CAS  PubMed  Google Scholar 

  14. Caponigro F, French RC, Kaye SB (1997) Protein kinase C: a worthwhile target for anticancer drugs? Anticancer Drugs 8:26–33

    Article  CAS  PubMed  Google Scholar 

  15. Buxton IL (2006) Pharmacokinetics: the dynamics of drug absorption, distribution, and elimination. In: Burnton LL, Lazo SL, Parker KL (eds) Goodman & Gilman’s the pharmacological basis of therapeutics, 10th edn. McGraw-Hill, New York, NY

    Google Scholar 

  16. Boroujerdi M (2002) Pharmacokinetics: principles and applications. McGraw-Hill, New York, NY, pp 343–367

    Google Scholar 

  17. Shargel L, Yu ABC (1999) Applied biopharmaceutics and pharmacokinetics, 4th edn. Appleton & Lange, Norwalk, CT, pp 573–605

    Google Scholar 

  18. Borst P, Elferink RO (2002) Mammalian abc transporters in health and disease. Annu Rev Biochem 71:537–592

    Article  CAS  PubMed  Google Scholar 

  19. Gottesman MM, Fojo T, Bates SE (2002) Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2:48–58

    Article  CAS  PubMed  Google Scholar 

  20. Jamieson GP, Snook MB, Bradley TR et al (1989) Transport and metabolism of 1-beta-D-arabinofuranosylcytosine in human ovarian adenocarcinoma cells. Cancer Res 49:309–313

    CAS  PubMed  Google Scholar 

  21. Mackey JR, Yao SY, Smith KM et al (1999) Gemcitabine transport in Xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst 91:1876–1881

    Article  CAS  PubMed  Google Scholar 

  22. Moscow JA (1998) Methotrexate transport and resistance. Leuk Lymphoma 30:215–224

    CAS  PubMed  Google Scholar 

  23. Kalman S, Metcalf K, Eintrei C (1997) Morphine, morphine-6-glucuronide, and morphine-3-glucuronide in cerebrospinal fluid and plasma after epidural administration of morphine. Reg Anesth 22:131–136

    Article  CAS  PubMed  Google Scholar 

  24. Goetz MP, Knox SK, Suman VJ, Rae JM, Safgren SL et al (2007) The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat 101(1):113–121

    Article  CAS  PubMed  Google Scholar 

  25. Schorth W, Goetz MP, Hamann U, Fasching PA et al (2009) Association between CYP2D6 polymorphisms and outcomes among women with early stage cancer treated with tamoxifen. JAMA 302(13):1429–1436

    Article  Google Scholar 

  26. Innocenti F, Iyer L, Ratain MJ (2001) Pharmacogenetics of anticancer agents: lessons from amonafide and irinotecan. Drug MetabDispos 29:596–600

    CAS  Google Scholar 

  27. Bachmann KA, Belloto RJ Jr (1999) Differential kinetics of phenytoin in elderly patients. Drugs Aging 15:235–250

    Article  CAS  PubMed  Google Scholar 

  28. Bruno R, Vivier N, Veyrat-Follet C, Montay G, Rhodes GR (2001) Population pharmacokinetics and pharmacokinetic–pharmacodynamic relationships for docetaxel. Invest New Drugs 19:163–169

    Article  CAS  PubMed  Google Scholar 

  29. Meibohm B, Derendorf H (1997) Basic concepts of pharmacokinetic/pharmacodynamic (PK/PD) modelling. Int J Clinpharmacol Ther 35:401–413

    CAS  Google Scholar 

  30. Sekine I, Saijo N (2001) Polymorphisms of metabolizing enzymes and transporter proteins involved in the clearance of anticancer agents. Ann Oncol 12:1515–1525

    Article  CAS  PubMed  Google Scholar 

  31. Roden DM, George AL Jr (2002) The genetic basis of variability in drug responses. Nat Rev Drug Discov 1:37–44

    Article  CAS  PubMed  Google Scholar 

  32. Evans WE, Johnson JA (2001) Pharmacogenomics: the inherited basis for interindividual differences in drug response. Annu Rev Genom Hum Genet 2:9–39

    Article  CAS  Google Scholar 

  33. Nolin TD (2008) Altered nonrenal drug clearance in ESRD. CurrOpinNephrolHypertens 17(6):555–559

    CAS  Google Scholar 

  34. Frye RF, Fitzgerald SM et al (2004) Effect of St John’s wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 76(4):323–329

    Article  CAS  PubMed  Google Scholar 

  35. Mathijssen RH, Verweij J, de Bruijn P et al (2002) Effects of St. John’s wort on irinotecan metabolism. J Natl Cancer Inst 91(16):1247–1249

    Article  Google Scholar 

  36. Lotsch J, Skarke C, Grosch S, Darimont J, Schmidt H, Geisslinger G (2002) The polymorphism A118G of the human mu-opioid receptor gene decreases the pupil constrictory effect of morphine-6-glucuronide but not that of morphine. Pharmacogenetics 12:3–9

    Article  CAS  PubMed  Google Scholar 

  37. Monzo M, Rosell R, Sanchez JJ et al (1999) Paclitaxel resistance in non-small-cell lung cancer associated with beta-tubulin gene mutations. J Clin Oncol 17:1786–1793

    CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Section of Clinical Pharmacology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Hinman Box 7506, One Medical Center Drive, Lebanon, NH, 03756, USA

    Uday B. Dandamudi M.B.B.S. & Lionel D. Lewis M.B., B.Ch., M.D., F.R.C.P. (London)

  2. Clinical Research, Myriad Pharmaceuticals, 305 Chipeta Way, Salt Lake City, UT, 84108, USA

    Andrew Beelen R.Ph., M.D.

Authors
  1. Uday B. Dandamudi M.B.B.S.
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  2. Andrew Beelen R.Ph., M.D.
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  3. Lionel D. Lewis M.B., B.Ch., M.D., F.R.C.P. (London)
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Corresponding author

Correspondence to Lionel D. Lewis M.B., B.Ch., M.D., F.R.C.P. (London) .

Editor information

Editors and Affiliations

  1. Sidney Kimmel Comprehensive Cancer Cente, Baltimore, Maryland, USA

    Michelle A. Rudek

  2. Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA

    Cindy H. Chau

  3. Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA

    William D. Figg

  4. Moffitt Cancer Center, Tampa, Florida, USA

    Howard L. McLeod

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Dandamudi, U.B., Beelen, A., Lewis, L.D. (2014). Anticancer Clinical Pharmacology Overview. In: Rudek, M., Chau, C., Figg, W., McLeod, H. (eds) Handbook of Anticancer Pharmacokinetics and Pharmacodynamics. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9135-4_9

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  • DOI: https://doi.org/10.1007/978-1-4614-9135-4_9

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-9134-7

  • Online ISBN: 978-1-4614-9135-4

  • eBook Packages: MedicineMedicine (R0)

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