Abstract

This modified grant proposal develops methods to address the complexity of modern Pharmacokinetics/Pharmacodynamics (PKPD) population studies focusing on computational PKPD and modeling of complex PKPD systems.
AIM 1, Statistical Estimation Methods for Population PK/PD Data, develops improved estimation methods for population PKPD models, and general methods to incorporate patients compliance behavior and uncertain dosing history into PKPD models.
AIM 2, Modeling System- PKPD, proposes two specific projects modeling system level PKPD across multiple organs, in particular for Cocaine/Nicotine PKPD and addiction dynamics modeling, and drug absorption physiological modeling.
AIM 3, Population Stochastic Differential Equations (SDE), investigates novel approaches to population model building that are based on the use of stochastic differential equation, in particular investigating methodology to include covariates into population PKPD modelsm, and apply SDE to drug-absortion modeling.

Public Health Relevance

of the research we propose consists in providing state of the art methodology to aid in the development of drugs, increasing the understanding of their pharmacokinetcs and pharmacodynamics, and the factors that explain their action in populations and individuals.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM026676-28
Application #
7582461
Study Section
Special Emphasis Panel (ZRG1-HOP-T (02))
Program Officer
Okita, Richard T
Project Start
1979-09-01
Project End
2011-08-31
Budget Start
2009-09-15
Budget End
2010-08-31
Support Year
28
Fiscal Year
2009
Total Cost
$115,232
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Frymoyer, Adam; Meng, Lina; Bonifacio, Sonia L et al. (2013) Gentamicin pharmacokinetics and dosing in neonates with hypoxic ischemic encephalopathy receiving hypothermia. Pharmacotherapy 33:718-26
Frymoyer, A; Lee, S; Bonifacio, S L et al. (2013) Every 36-h gentamicin dosing in neonates with hypoxic-ischemic encephalopathy receiving hypothermia. J Perinatol 33:778-82
Frame, Bill; Beal, Stuart L; Miller, Raymond et al. (2007) Mixed effects modeling of weight change associated with placebo and pregabalin administration. J Pharmacokinet Pharmacodyn 34:753-70
Levi, Micha; Dempsey, Delia A; Benowitz, Neal L et al. (2007) Population pharmacokinetics of nicotine and its metabolites I. Model development. J Pharmacokinet Pharmacodyn 34:5-21
Levi, Micha; Dempsey, Delia A; Benowitz, Neal L et al. (2007) Prediction methods for nicotine clearance using cotinine and 3-hydroxy-cotinine spot saliva samples II. Model application. J Pharmacokinet Pharmacodyn 34:23-34
Beal, Stuart L (2005) Conditioning on certain random events associated with statistical variability in PK/PD. J Pharmacokinet Pharmacodyn 32:213-43
Zhang, Liping; Sheiner, Lewis B (2005) Analyzing multi-response data using forcing functions. J Pharmacokinet Pharmacodyn 32:283-305
Soy, Dolors; Beal, Stuart L; Sheiner, Lewis B (2004) Population one-compartment pharmacokinetic analysis with missing dosage data. Clin Pharmacol Ther 76:441-51
Kenna, Leslie A; Sheiner, Lewis B (2004) Estimating treatment effect in the presence of non-compliance measured with error: precision and robustness of data analysis methods. Stat Med 23:3561-80
Zhang, Liping; Beal, Stuart L; Sheinerz, Lewis B (2003) Simultaneous vs. sequential analysis for population PK/PD data II: robustness of methods. J Pharmacokinet Pharmacodyn 30:405-16

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