Pharmacokinetic physiological

Charnick SB, Kawai R, Nedelman JR, Lemaire M, Niederberger W, Sato H. Perspectives in pharmacokinetics. Physiologically based pharmacokinetic modeling as atoolfor drug development./P/jarmacokmefTEop/jarm 1995 Apr 23(2) 217-29. Review. 

Charnik, S.B., Kawai, R., Nefelman, J.R., Lemaire, M., Niederberger, W. and Sato, H. (1995) Perspectives in pharmacokinetics. Physiologically-based pharmacokinetic modeling as a tool for drug development. Journal of Pharmacokinetics and Biopharmaceutics, 23, 231-235. 

Factors Affecting Theophylline Pharmacokinetics Physiological Perturbations... 

Pharmacodynamics is the study of dmg action primarily in terms of dmg stmcture, site of action, and the biochemical and physiological consequences of the dmg action. The availabiUty of a dmg at its site of action is deterrnined by several processes (Fig. 1), including absorption, metaboHsm, distribution, and excretion. These processes constitute the pharmacokinetic aspects of dmg action. The onset, intensity, and duration of dmg action are deterrnined by these factors as well as by the avadabihty of the dmg at its receptor site(s) and the events initiated by receptor activation (see Drug delivery). 

The realization of sensitive bioanalytical methods for measuring dmg and metaboUte concentrations in plasma and other biological fluids (see Automatic INSTRUMENTATION BlosENSORs) and the development of biocompatible polymers that can be tailor made with a wide range of predictable physical properties (see Prosthetic and biomedical devices) have revolutionized the development of pharmaceuticals (qv). Such bioanalytical techniques permit the characterization of pharmacokinetics, ie, the fate of a dmg in the plasma and body as a function of time. The pharmacokinetics of a dmg encompass absorption from the physiological site, distribution to the various compartments of the body, metaboHsm (if any), and excretion from the body (ADME). Clearance is the rate of removal of a dmg from the body and is the sum of all rates of clearance including metaboHsm, elimination, and excretion. 

Absorption, distribution, biotransformation, and excretion of chemical compounds have been discussed as separate phenomena. In reality all these processes occur simultaneously, and are integrated processes, i.e., they all affect each other. In order to understand the movements of chemicals in the body, and for the delineation of the duration of action of a chemical m the organism, it is important to be able to quantify these toxicokinetic phases. For this purpose various models are used, of which the most widely utilized are the one-compartment, two-compartment, and various physiologically based pharmacokinetic models. These models resemble models used in ventilation engineering to characterize air exchange. 

Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models... 

Note This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by inhalation, or by ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 

Andersen ME, Clewell HJ 3rd, Gargas ME, et al. 1987. Physiologically based pharmacokinetics and the risk assessment process for methylene chloride. Toxicol Appl Pharmacol 87 185-205. 

Krishnan K, Andersen ME, Clewell H 3rd, et al. 1994. Physiologically based pharmacokinetic modeling of chemical mixtures. In Yang R, ed. Toxicology of chemical mixtures. New York, NY Academic Press, 399-437. 

Leung H-W. 1993. Physiologically-based pharmacokinetic modelling. In Ballentine B, Marro T, Turner P, eds. General and applied toxicology. New York, NY Stockton Press, 153-164. 

Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent chemical or metabolite in an animal system. There are two types of pharmacokinetic models data-based and physiologically-based. A data-based model divides the animal system into a series of compartments which, in general, do not represent real, identifiable anatomic regions of the body whereby the physiologically-based model compartments represent real anatomic regions of the body. 

Andersen ME, MacNaughton MG, Clewell HJ, et al. 1987. Adjusting exposure limits for long and short exposure periods using a physiological pharmacokinetic model. Am Ind Hyg Assoc J 48(4) 335-343. 

KrishnanK, Andersen ME. 1994. Physiologically-based pharmacokinetic modeling in toxicology. In Wallace Hayes, ed. Principles and methods of toxicology. 3rd edition. New York, NY Raven Press, Ltd. 

Physiologically Based Pharmacokinetic (PBPK) Model—is comprised of a series of compartments representing organs or tissue groups with realistic weights and blood flows. These models require a variety of physiological information tissue volumes, blood flow rates to tissues, cardiac output, alveolar ventilation rates and, possibly membrane permeabilities. The models also utilize biochemical information such as air/blood partition coefficients, and metabolic parameters. PBPK models are also called biologically based tissue dosimetry models. 

Simulation methods have also been developed that include physiologically based pharmacokinetic modeling (PBPK) and methods such as Cloe PK, OMPPPlus, GastroPlus , SimCYP , and others [122] that are described elsewhere in this book. It is likely that the computational metabolism predictions could be integrated with these to assist in deriving more accurate predictions of human pharmacokinetic parameters. 

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