Abstract

Drug therapy for many problems (cancer, AIDS, infectious disease, transplants, cardiovascular disease, stroke, etc.) is limited too often by drug toxicity. Therapy can be optimized for an individual patient by describing quantitatively the relationships between dose, drug exposure (serum levels and/or area under the serum level curve, AUQ and effect, such as bacterial, viral and cancel cell growth and killing, as described by Zhi (and many other) models, as well as those between drug exposure and toxicity. Development of dose-exposureeffect relationships allows rational selection of target therapeutic goals such as serum drug levels or profiles, or drug effects, and thus permits dosing to proceed optimally, and with optimal precision in their achievement. The barrier to such optimized drug therapy has been the lack of dose-concentration-effect relationships developed from populations of patients studied in their relevant real-life clinical care situations. Population pharmacokinetic and dynamic modeling is the tool to remove this barrier.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR012609-05
Application #
6569239
Study Section
Project Start
2002-03-01
Project End
2003-02-28
Budget Start
Budget End
Support Year
5
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Type
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Telford, Dawn E; Lipson, Sara M; Barrett, P Hugh R et al. (2005) A novel inhibitor of oxidosqualene:lanosterol cyclase inhibits very low-density lipoprotein apolipoprotein B100 (apoB100) production and enhances low-density lipoprotein apoB100 catabolism through marked reduction in hepatic cholesterol content. Arterioscler Thromb Vasc Biol 25:2608-14
Dash, Ranjan K; Bell, Bradley M; Kushmerick, Martin J et al. (2005) Estimating in vitro mitochondrial oxygen consumption during muscle contraction and recovery: a novel approach that accounts for diffusion. Ann Biomed Eng 33:343-55
Dodds, Michael G; Hooker, Andrew C; Vicini, Paolo (2005) Robust population pharmacokinetic experiment design. J Pharmacokinet Pharmacodyn 32:33-64
Spilker, Mary E; Seng, Kok-Yong; Yao, Amy A et al. (2005) Mixture model approach to tumor classification based on pharmacokinetic measures of tumor permeability. J Magn Reson Imaging 22:549-58
Lukas, J C; Suarez, A M; Valverde, M P et al. (2005) Time-dependent pharmacokinetics of cyclosporine (Neoral) in de novo renal transplant patients. J Clin Pharm Ther 30:549-57
Welty, Francine K; Lichtenstein, Alice H; Barrett, P Hugh R et al. (2004) Interrelationships between human apolipoprotein A-I and apolipoproteins B-48 and B-100 kinetics using stable isotopes. Arterioscler Thromb Vasc Biol 24:1703-7
Calvo, R; Telletxea, S; Leal, N et al. (2004) Influence of formulation on propofol pharmacokinetics and pharmacodynamics in anesthetized patients. Acta Anaesthesiol Scand 48:1038-48
Tannock, L R; Little, P J; Tsoi, C et al. (2004) Thiazolidinediones reduce the LDL binding affinity of non-human primate vascular cell proteoglycans. Diabetologia 47:837-43
Foracchia, Marco; Hooker, Andrew; Vicini, Paolo et al. (2004) POPED, a software for optimal experiment design in population kinetics. Comput Methods Programs Biomed 74:29-46
Whitfield, A J; Marais, A D; Robertson, K et al. (2003) Four novel mutations in APOB causing heterozygous and homozygous familial hypobetalipoproteinemia. Hum Mutat 22:178

Showing the most recent 10 out of 77 publications