Modeling drug-protein dynamics

Lambertus A. Peletier

doi:10.3934/dcdss.2012.5.191

Article Contents

2012, Volume 5, Issue 1: 191-207. Doi: 10.3934/dcdss.2012.5.191

This issue Previous Article Stripe patterns and the Eikonal equation Next Article Stability of the steady state for multi-dimensional thermoelastic systems of shape memory alloys

Modeling drug-protein dynamics

Lambertus A. Peletier^1,

1.
Mathematical Institute, Leiden University, PB 9512, 2300 RA Leiden

Received: March 2009

Revised: January 2010

Published: February 2012

Abstract Related Papers Cited by

Abstract

In this paper we discuss two models involving protein binding. The first model describes a system involving a drug, a receptor and a protein, and the question is to what extent the affinity of the drug to the protein affects the drug-receptor binding and thereby the efficiency of the drug. The second model is the basic model underlying Target-Mediated Drug Disposition, which describes the pharmacokinetics of a drug in the presence of a target, often a receptor.

Keywords:

Mathematics Subject Classification: Primary: 34C20, 34D15; Secondary: 92C42, 92C45, 80A30.

Citation:

Related Papers

Cited by

References

[1]	D. J. A. Crommelin (ed), Robert D. Sindelar (ed) and Bernd Meibohm (ed), "Pharmaceutical Biotechnology: Fundamentals and Applications," Informa Healthcare, 2008.
[2]	L. Gibiansky, E. Gibiansky, T. Kakkar and P. Ma, Approximations of the target-mediated drug disposition model and identifiability of model parameters, J. Pharmacokinet. Phamacodyn., 35 (2008), 573-591.doi: 10.1007/s10928-008-9102-8.
[3]	T. Kenakin, "A Pharmacology Primer: Theory, Application and Methods," Elsevier Academic Press, 2004.
[4]	B.-F. Krippendorff, K. Kuester, C. Kloft and W. Huisinga, Nonlinear pharmacokinetics and therapeutic proteins resulting from receptor-mediated endocytosis, J. Pharmacokinet. Phamacodyn., 36 (2009,) 239-260.
[5]	G. Levy, Pharmacologic target mediated drug disposition, Clin. Pharmacol. Ther., 56 (1994), 248-252.doi: 10.1038/clpt.1994.134.
[6]	D. E. Mager, Target-mediated drug disposition and dynamics, Biochem. Pharmacology, 72 (2006), 1-10.doi: 10.1016/j.bcp.2005.12.041.
[7]	D. E. Mager and W. J. Jusko, General pharmacokinetic model for drugs exhibiting target-mediated drug disposition, J. Pharmacokinet. Phamacodyn., 28 (2001), 507-532.doi: 10.1023/A:1014414520282.
[8]	D. E. Mager and W. Krzyzanski, Quasi-equilibrium pharmacokinetic model for drugs exhibiting target-mediated drug disposition, Pharm. Research, 22 (2005), 1589-1596.doi: 10.1007/s11095-005-6650-0.
[9]	B. K. Martin, Kinetics of elimination of drugs possessing high affinity for the plasma proteins, Nature, 207 (1965), 959-960.doi: 10.1038/207959a0.
[10]	B. Meibohm (ed), "Pharmacokinetics and Pharmacodynamics of Biotech Drugs: Principles and Case Studies in Drug Development," Wiley-VCH Verlag GmbH & Co KGaA, Weinheim, Germany, 2006.
[11]	L. A. Peletier, N. Benson and P. H. van der Graaf, Impact of plasma-protein binding on receptor occupancy: An analytical description, J. Theor. Biology, 256 (2009), 253-262.doi: 10.1016/j.jtbi.2008.09.014.
[12]	L. A. Peletier and J. Gabrielsson, Dynamics of target-mediated drug disposition, Eur. J. of Pharm. Sci., 38 (2009), 445-464.doi: 10.1016/j.ejps.2009.09.007.
[13]	R. L. Rich, Y. S. Day, T. A. Morton, D. G. Myszka, High-resolution and high-throughput protocols for measuring drug/Human Serum Albumin interactions using BIACORE, Anal. Biochem., 296 (2001), 197-207.doi: 10.1006/abio.2001.5314.
[14]	Y. Sugiyama and M. Hanano, Receptor-mediated transport of peptide hormones and its importance in the overall hormone disposition in the body, Pharm. Research, 6 (1989), 192-202.doi: 10.1023/A:1015905331391.
[15]	G. L. Trainor, The importance of plasma protein binding in drug discovery, Expert Opin. Drug. Discov., 2 (2007), 51-64.doi: 10.1517/17460441.2.1.51.
[16]	J. G. Wagner, A new generalised nonlinear pharmacokinetic model and its implications, in J. G. Wagner (ed), Biopharmaceutics and relevant pharmacokinetics, Drug Intelligence Publications, Hamilton, pp. 302-317, (1971).