POPULATION ANALYSIS IS THE METHODOLOGY USED TO QUANTIFY INTERSUBJECT VARIABILITY IN KINETIC STUDIES. IN THIS RESEARCH PROJECT, WE PROPOSE TO DEVELOP A GENERAL POPULATION ANALYSIS PACKAGE, AND TO INTERFACE THIS PACKAGE WITH THE CURRENT SAAM II MODELING PROGRAM. THIS PACKAGE COULD TYPICALLY BE USED FOR THE POPULATION MODELING OF PHARMACO-KINETIC/PHARMACODYNAMIC SYSTEMS AND TRACER KINETIC SYSTEMS. POPULATION ANALYSIS IS WIDELY USED IN PHARMACOKINETIC STUDIES SINCE IT IS THE KEY TO UNDERSTANDING HOW DRUGS BEHAVE IN HUMANS AND ANIMALS. IT PROVIDES THE FOUNDATION FOR THE INTELLIGENT DESIGN OF DOSAGE REGIMENS TO TREAT DISEASE PROCESSES. IN METABOLIC STUDIES, IT IS USED TO IDENTIFY WHICH PARAMETERS IN A MODEL CHANGE WHEN A POPULATION OF NORMAL SUBJECTS IS COMPARED TO A POPULATION OF SUBJECTS WITH A KNOWN PATHOLOGICAL CONDITION. RFKA IS SUPPORTING THE INITIAL DEVELOPMENT OF A PROTOTYPE FOR THE PARAMETRIC METHOD; THIS IS CURRENTLY BEING TESTED USING SIMPLE BUT STANDARD PHARMACOKINETIC MODELS. AN R-01 HAS BEEN SUBMITTED TO SUPPORT THE FULL DEVELOPMENT AND IMPLEMENTATION OF A POPULATION ANALYSIS MODULE.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR002176-10
Application #
5223831
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1996
Total Cost
Indirect Cost
Wolfe, B M; Barrett, P H; Laurier, L et al. (2000) Effects of continuous conjugated estrogen and micronized progesterone therapy upon lipoprotein metabolism in postmenopausal women. J Lipid Res 41:368-75
Vicini, P; Zachwieja, J J; Yarasheski, K E et al. (1999) Glucose production during an IVGTT by deconvolution: validation with the tracer-to-tracee clamp technique. Am J Physiol 276:E285-94
Parhofer, K G; Barrett, P H; Schwandt, P (1999) Low density lipoprotein apolipoprotein B metabolism: comparison of two methods to establish kinetic parameters. Atherosclerosis 144:159-66
Vicini, P; Caumo, A; Cobelli, C (1999) Glucose effectiveness and insulin sensitivity from the minimal models: consequences of undermodeling assessed by Monte Carlo simulation. IEEE Trans Biomed Eng 46:130-7
Burnett, J R; Wilcox, L J; Telford, D E et al. (1999) The magnitude of decrease in hepatic very low density lipoprotein apolipoprotein B secretion is determined by the extent of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition in miniature pigs. Endocrinology 140:5293-302
Vicini, P; Cobelli, C (1999) A priori identifiability of distributed models of blood-tissue exchange. Ann Biomed Eng 27:200-7
Cobelli, C; Caumo, A; Omenetto, M (1999) Minimal model SG overestimation and SI underestimation: improved accuracy by a Bayesian two-compartment model. Am J Physiol 277:E481-8
Bertoldo, A; Vicini, P; Sambuceti, G et al. (1998) Evaluation of compartmental and spectral analysis models of [18F]FDG kinetics for heart and brain studies with PET. IEEE Trans Biomed Eng 45:1429-48
Barrett, P H; Bell, B M; Cobelli, C et al. (1998) SAAM II: Simulation, Analysis, and Modeling Software for tracer and pharmacokinetic studies. Metabolism 47:484-92
Cobelli, C; Caumo, A (1998) Using what is accessible to measure that which is not: necessity of model of system. Metabolism 47:1009-35

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