Abstract
Pharmacokinetic models are used to describe or predict the time-dependent changes in drug concentration in blood and tissues, i.e., concentration × time (C × t) curves. There are two basic approaches to pharmacokinetic modelling. In the first, empirical or compartmental models are derived using curve-fitting programs to provide a mathematical description of C × t data. In the second, physiologically based pharmacokinetic (PBPK) models are constructed based on anatomical and physiological data from animals and humans, incorporating physi-cochemical data on a specific drug or chemical. Unlike empirical or compartmental pharmacokinetic models, PBPK models are physiologically realistic, bringing a biological basis to the mathematical description of a compound’s pharmacokinetics. Until relatively recently, the utility of PBPK modelling had been limited by the computational intensity of the PBPK approach and the availability of adequate computer hardware and software. In recent years, however, PBPK modelling has become a practical tool for the study of a variety of pharmacological and toxicological problems (Bischoff et al, 1971; Gerlowski and Jain, 1983).
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References
Abramson, D.I. (1967) Circulation in the extremities, Academic Press, New York.
Adlkofer, F., Scherer, G., Jarczyk, L. et al(1988) Pharmacokinetics of 3’- hydroxycotinine, in Pharmacology of Nicotine, ICSU Symposium Series, 9, 25–8.
Andersen, M.E. (1989) Tissue dosimetry, physiologically based pharmacokinetic modeling, and cancer risk assessment. Cell Biol and Toxicol, 5, 405–16.
Ariens, E.J., and Simonis, A.M. (1964) A molecular basis for drug action. The interaction of one or more drugs with different receptors. J. Pharm. Pharmacol, 16, 289–312.
Benowitz, N.L. (1988) Pharmacokinetics and pharmacodynamics of nicotine, in Pharmacology of Nicotine, ICSU Symposium Series, 9.
Benowitz, N.L. and Jacob, P. III. (1985) Metabolism, pharmacokinetics and pharmacodynamics of nicotine in man, in Tobacco Smoking and Nicotine: A Neuro-biological Approach, (Eds E.T. Iwamoto and L. David ), Plenum Press, New York.
Benowitz, N.L., Jacob, P. III, Jones, R.T. et al(1982) Interindividual variability in the metabolism and cardiovascular effects of nicotine in man. J. Pharmacol Exp. Ther., 221, 368–72.
Benowitz, N.L., Kuyt, F., Jacob, P. III et al(1983) Cotinine disposition and effects. Clin. Pharmacol Ther., 34, 604–11.
Bischoff, K.B., Dedrick, R.L., Zaharko, D.S. et al(1971) Methotrexate pharmacokinetics. J. Pharm. Sci., 60, 1128–33.
Curvall, M., Elwin, C.E., Kazemi-Vala, E. et al(1990a) The pharmacokinetics of cotinine in plasma and saliva from non-smoking healthy volunteers. Eur. J. Clin. Pharmacol, 38, 281–7.
Curvall, M., and Enzell, C.R. (1986) Monitoring absorption by means of determination of nicotine and cotinine. Arch. Toxicol Suppl, 9, 88–102.
Curvall, M., Kazemi-Vala, E., and Enzell, C.R. (1982) Simultaneous determination of nicotine and cotinine in plasma using capillary column gas chromatography with nitrogen sensitive detection. J. Chromatogr. Biomed. Appl, 232, 283–93.
Curvall, M., Kazemi-Vala, E., Enzell, C.R. et al(1990b) Simulation and evaluation of nicotine intake during passive smoking: cotinine measurements in body fluids of nonsmokers given intravenous infusions of nicotine. Clin. Pharmacol Ther., 47, 42–9.
Davis, N.R. and Mapleson, W.W. (1981) Structure and quantification of a physiological model of the distribution of injected agents and inhaled anaesthetics. Br. J. Anaesth., 53, 399–404.
deBethizy, J.D., and Andersen, M.E. (1990) A physiologically based pharmacokinetic (PB-PK) model for nicotine in the rat (Abstract). Toxicologist, 10, 862.
DeSchepper, P.J., Hecken, A.V., Daenens, P. et al(1987) Kinetics of cotinine after oral and intravenous administration to man. Eur. J. Clin. Pharmacol, 31, 583–58.
D’Souza, R.W. and Boxenbaum, H. (1988) Physiological pharmacokinetic models: some aspects of theory, practice and potential. Toxicol Ind. Health, 4, 151–71.
Feyerabend, C., Ings, R.M.J., and Russell, M.A.H. (1985) Nicotine pharmacokinetics and its application to intake from smoking. Br. J. Clin. Pharmacol, 19, 239–47.
Gabrielsson, J. and Bondesson, U. (1987) Constant-rate infusion of nicotine and cotinine. I. A physiological pharmacokinetic analysis of the cotinine disposition, and effects on clearance and distribution in the rat. J. Pharmacokin. Biopharm., 15, 583–99.
Galeazzi, R.L. Daenens, P. and Gugger, M. (1985) Steady-state concentration of cotinine as a measure of nicotine-intake by smokers. Eur. J. Clin. Pharmacol. 28, 301 - 4.
Gastonguay, M.R., Baiter, N.J. and Schwartz, S.L. (1990) A physiologically-based pharmacokinetic (PBPK) model of nicotine and three metabolites (Abstract). Pharmacologist, 32, 141.
Gerlowski, L.E. and Jain, R.K. (1983) Physiologically based pharmacokinetic modeling: principles and applications. J. Pharm. Sci., 72, 1103–25.
Jacob, P., III, Benowitz, N.L. and Shulgin, A.T. (1988) Recent studies of nicotine metabolism in humans. Pharmacol. Biochem. Behav., 30, 249–53.
Kyerematen, G.A., Damiano, M.D., Dvorchik, B.H. et al.(1982) Smoking-induced changes in nicotine disposition: application of a new HPLC assay for nicotine and its metabolites. Clin. Pharmacol. Ther., 32, 769–80.
Kyerematen, G.A., Morgan, M.L., Chattopadhyay, B. et al.(1990) Disposition of nicotine and eight metabolites in smokers and nonsmokers: identification in smokers of two metabolites that are longer lived than cotinine. Clin. Pharmacol. Ther., 48, 641–51.
Leggett, R.W. and Williams, L.R. (1991) Suggested reference values for regional blood volumes in humans. Health Physics, 60, 139–54.
Lewis, E.A., Tang, H., Gunther, K. et al.(1990) Use of urine nicotine and cotinine measurements to determine exposure of nonsmokers to sidestream tobacco smoke. Indoor Air ‘80. International Conference on Indoor Air Quality and Climate. Ottawa, 151–6.
Notari, R.E. (1987) Biopharmaceutics and clinical pharmacokinetics. 4th ed. Marcel Dekker Inc., New York, 49.
Plowchalk, D.R. and deBethizy, J.D. (1991) A PB-PK model for nicotine tissue and plasma kinetics in the Sprague-Dawley rat (Abstract). Toxicologist 11, 280.
Plowchalk, D.R., Fluhler, E.N. Lipiello, P.M. et al.(1992) A biologically-based model for nicotinic receptor dynamics in the rat brain (Abstract). Toxicologist, 293.
Porchet, H.C., Benowitz, N.L. and Sheiner, L.B. (1988) Pharmacodynamic model of tolerance: application to nicotine. Pharmacol. Exp. Ther., 244, 231–6.
Porchet, H.C., Benowitz, N.L., Sheiner, L.B. et al(1987) Apparent tolerance to the acute effect of nicotine results in part from distribution kinetics. J. Clin. Invest., 80, 1466–71.
Quiring, D.P. (1949) Collateral circulation: anatomical aspects, Lea and Febiger, Philadelphia.
Robinson, D.E., Baiter, N.J. and Schwartz, S.L. (1992) A physiologically-based pharmacokinetic model for nicotine and cotinine in man. J. Pharmacokin. Biopharm., 20, 591–609.
Rothe, C.F. (1984) Venous system: physiology of the capacitance vessels, in Handbook of Physiology, Section 2 Volume III (Ed. J.T. Shepherd ), Waverly Press, Baltimore, 397.
Rothe, C.F. (1984) Venous system: physiology of the capacitance vessels, in Handbook of Physiology, Section 2 Volume III (Ed. J.T. Shepherd ), Waverly Press, Baltimore, 397.
Scheiner, L.B. (1989) Clinical pharmacology and the choice between theory and empiricism. Clin. Pharmacol. Ther., 6, 605–15.
Scherer, G. Jaczy, L. Heller, W.D. et al.(1988) Pharmacokinetics of nicotine, cotinine, and 3’-hydroxycotinine in cigarette smokers. Klin. Wochenschr., 66(suppl XI), 5–11.
Schievelbein, H. (1982) Nicotine, resorption and fate. Pharmacol. Ther., 18, 233–48.
Schwartz. S.L., Ball, R.T. and Witorsch, P. (1987) Mathematical modelling of nicotine and cotinine as biological markers of environmental tobacco smoke exposure. Tox. Let., 35, 53–8.
Sebalt, R.J. and Kreeft, J.H. (1987) Efficient pharmacokinetic modeling of complex clinical dosing regimens: the universal elementary dosing regimen and computer algorithm EDFAST. J. Pharm. Sci., 76, 93–100.
Williams, L.R. and Leggett, R.W. (1989) Resting values for resting blood flow to organs of man. Clin. Phys. Physiol. Meas., 10, 187–217.
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Schwartz, S.L., Gastonguay, M.R., Robinson, D.E., Balter, N.J. (1993). Physiologically based pharmacokinetic modelling of nicotine. In: Gorrod, J.W., Wahren, J. (eds) Nicotine and Related Alkaloids. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-2110-1_12
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DOI: https://doi.org/10.1007/978-94-011-2110-1_12
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