Abstract
A development project starts with someone identifying in a patient population an unmet medical need, which may offer a business opportunity. Even when successful treatments are available for the target disease, a medical need may exist when standard treatments fail or unacceptable adverse events (AE) occur after longtime treatment. Typical for such situation is that a sound knowledge of the disease progression is available. The mechanism of action of a new drug is crucial to develop the pharmacodynamic model of the target drug action. Combining the disease model with the pharmacodynamics and the pharmacokinetics of the new drug allowed us to optimize the pivotal clinical study, confirming the efficacy in the target patient population.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References and Further Reading
Arnett FC, Edworthy SM, Bloch DA, Mcshane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA Jr, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG (1988) The American rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324
Balant LP, Aarons L (eds) (1997) The population approach: measuring and managing variability in response, concentration and dose. Commission of the European communities, European cooperation in the field of scientific and technical research (COST B1). European Commission, Brussels
Bohl E (2006) Mathematik in der Biologie, 4th edn. Springer, Berlin
Collett D (2003) Modelling binary data. Chapman and Hall, London
Danhof M, Steimer JL (eds) (1998) Advances in simultaneous pharmacokinetic/pharmacodynamic modelling, measurement and kinetics of in vivo drug effects. Commission of the European communities, European cooperation in the field of scientific and technical research (COST B1). European Commission, Brussels
Groß J (2010) Logistische regression. In: Grundlegende statistik mit R. Vieweg+Teubner, Wiesbaden, p 224
Horn W, Oed C (2003) Comparative trial of the efficacy and safety of leunomide 10 mg versus 20 mg daily doses in patients with active rheumatoid arthritis. Technical Report F2002CLN00017, Aventis Pharma, Frankfurt/Main
Lambertus A, Peletier JG, den Haag J (2005) A dynamical systems analysis of the indirect response model with special emphasis on time to peak response. J Pharmacokinet Pharmacodyn 32(3–4):607–654. PMID: 16307206
Mladenovic V, Domljan Z, Rozman B, Jajic I, Mihajlovic D, Dordevic J, Popovic M, Dimitrijevic M, Zivkovic M, Campion G (1995) Safety and effectiveness of leunomide in the treatment of patients with active rheumatoid arthritis results of a randomized, placebo-controlled, phase II study. Arthritis Rheum 38(11):1595–603
Poor G, Strand V (2004) Efficacy and safety of leunomide 10 mg versus 20 mg once daily in patients with active rheumatoid arthritis: multinational double-blind, randomized trial. Rheumatology (Oxford, England) 43(6):744–749. PMID: 15026583
Rozman B (2002) Clinical pharmacokinetics of leunomide. Clin Pharmacokinet 41(6):421–430
Weber W, Harnisch L (1997a) Population pharmacokinetic report, leunomide. Technical Report, Hoechst Marion Roussel
Weber W, Harnisch L (1997b) Use of a population approach to the development of leunomide: a new disease-modifying drug in the treatment of rheumatoid arthritis. In: Balant LP, Aarons L (eds) The population approach: measuring and managing variability in response, concentration and dose. Commission of the European communities, European cooperation in the field of scientific and technical research (COST B1). European Commission, Brussels
Weber W, Harnisch L (1998) Use of population PK/PD modelling to estimate the optimal dose regimen for treating active rheumatoid arthritis with leunomide. In: Danhof M, Steimer JL (eds) Advances in simultaneous pharmacokinetic/pharmacodynamic modelling, measurement and kinetics of in vivo drug effects. Commission of the European communities, European cooperation in the field of scientific and technical research (COST B1). European Commission, Brussels
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag Berlin Heidelberg
About this entry
Cite this entry
Weber, W. (2013). Typical PK/PD Approaches in Preclinical and Clinical Development. In: Vogel, H.G., Maas, J., Hock, F.J., Mayer, D. (eds) Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25240-2_51
Download citation
DOI: https://doi.org/10.1007/978-3-642-25240-2_51
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-25239-6
Online ISBN: 978-3-642-25240-2
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences