Physiological Aspects of Drug Kinetics and Dynamics

  • Gerald M. Woerlee
Part of the Developments in Critical Care Medicine and Anesthesiolgy book series (DCCA, volume 26)


Before discussing the pharmacokinetic and pharmacodynamic models in current use, it is well worth discussing their physiological basis. This has several advantages.
  • A physiological approach to drug kinetics describes the actual distribution and elimination of drugs.

  • Anesthesiologists usually view and solve most problems in physiological terms. Therefore such an approach is one which simplifies learning drug kinetics and dynamics by using familiar concepts.

  • An appreciation of the physiological basis of the currently used kinetic and dynamic models makes it easier to predict changes resulting from any disturbance of normal physiology.

  • An appreciation of the physiological basis of drug distribution and elimination also shows some of the limitations of current pharmacokinetic models.


Cardiac Output Pharmacokinetic Model Circulation Time Anesthetic Drug Drug Kinetic 


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  1. 1.
    Altman PL, et al., (eds.),“Handbook of Circulation”, pub. W.B. Saunders, U.S.A., 1959, Library of Congress No. 59-15183, pages 115–125.Google Scholar
  2. 2.
    Pappenheimer JR, et al: Filtration, diffusion and molecular sieving through peripheral capillary membranes. American Journal of Physiology, 1951: 167: 13–46.PubMedGoogle Scholar
  3. 3.
    Pappenheimer JR: Passage of molecules through capillary walls. Physiological Reviews, 1953: 33: 387–423.PubMedGoogle Scholar
  4. 4.
    Woerlee GM, “Common Perioperative Problems and the Anaesthetist”, published Kluwer Academic Publishers, the Netherlands, 1988, ISBN 0-89838-402-8, pages 508–510.Google Scholar
  5. 5.
    Apelblat A, et al: A mathematical analysis of capillary-tissue fluid exchange. Biorheology, 1974: 11: 1–49.PubMedGoogle Scholar
  6. 6.
    Renkin EM: Capillary permeability to lipid-soluble molecules. American Journal of Physiology, 1952: 168: 538–545.PubMedGoogle Scholar
  7. 7.
    Kotrly KJ, et al: First pass uptake of lidocaine, diazepam, and thiopental in the human lung. Anesthesia and Analgesia, 1988: 67: S119.Google Scholar
  8. 8.
    Roerig DK, et al: First pass uptake of fentanyl, meperidine, and morphine in the human lung. Anesthesiology, 1987: 67: 466–472.CrossRefPubMedGoogle Scholar
  9. 9.
    Taeger K, et al: Pulmonary kinetics of fentanyl and alfentanil in surgical patients. British Journal of Anaesthesia, 1988: 61:425–434.CrossRefPubMedGoogle Scholar
  10. 10.
    Taeger K, et al: Uptake of fentanyl by human lung. Anesthesiology, 1984: 61: A246.CrossRefGoogle Scholar
  11. 11.
    Weigand BD, et al: The use of indocyanine green for the evaluation of hepatic function and blood flow in man. American Journal of Digestive Diseases, 1960: 5: 427–436CrossRefGoogle Scholar
  12. 12.
    Gentzler RD, et al: Angiographic estimation of right ventricular volume in man. Circulation, 1974: 50: 324–330.PubMedGoogle Scholar
  13. 13.
    McNamee JE, Staub NC: Pore models of sheep lung microvascular barrier using new data on protein tracers. Microvascular Research, 1979: 18: 229–224.CrossRefPubMedGoogle Scholar
  14. 14.
    Brigham KL, Owen PJ: Mechanism of the serotonin effect on lung transvascular fluid and protein movement in awake sheep. Circulation Research, 1975: 36: 761–770.PubMedGoogle Scholar
  15. 15.
    Kennedy JW, et al:Quantitative angiography. I. The normal left ventricle in man. Circulation, 1966: 34: 272–278.PubMedGoogle Scholar
  16. 16.
    Slutsky R, et al: Pulmonary blood volume. Correlation of equilibrium radionucleotide and dye-dilution estimates. Investigative Radiology, 1982: 17: 233–240.PubMedGoogle Scholar
  17. 19.
    Wagner JG: “Fundamentals of Clinical Pharmacokinetics”, pub. Drug Intelligence Publications Inc., U.S.A. ISBN 0-914678-20-4, pages 124–125.Google Scholar
  18. 20.
    Diem, K., Lentner, C., “Wissenschaftliche Tabellen”, 7th edn., pub. CIBA-GEIGY A.G., Basel, 1968.Google Scholar
  19. 21.
    Bruce A, et al: Body composition. Prediction of normal body potassium, body water and body fat in adults on the basis of body height, body weight and age. Scandinavian Journal of Clinical & Laboratory Investigation, 1980: 40: 461–473.CrossRefGoogle Scholar
  20. 22.
    Moore FD, et al, “The Body Cell Mass and its Supporting Environment. Body Composition in Health and Disease.”, published W.B.Saunders Co., U.S.A., 1963, pages 167–168.Google Scholar
  21. 23.
    Staub NC: Pulmonary edema. Physiological Reviews, 1974: 54: 678–811.CrossRefPubMedGoogle Scholar
  22. 24.
    Aukland K, Nicolaysen G: Interstitial fluid volume: Local regulatory mechanisms. Physiological Reviews, 1981: 61: 556–643.PubMedGoogle Scholar
  23. 25.
    Holliday MA, et al: Factors that limit brain volume changes in response to acute and sustained hyper-and hyponatremia. Journal of Clinical Investigation, 1968: 47: 1916–1928.CrossRefPubMedGoogle Scholar
  24. 26.
    Wiegand BD, et al: The use of indocyanine green for the evaluation of hepatic function and blood flow in man. American Journal of Digestive Diseases, 1960: 5: 427–436.CrossRefPubMedGoogle Scholar
  25. 27.
    Caesar J, et al: The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clinical Science, 1961: 21: 43–57.PubMedGoogle Scholar
  26. 28.
    Goldring W, et al: Relations of effective renal blood flow and glomerular function to tubular excretory mass in normal man. Journal of Clinical Investigation, 1940: 19: 739–750.CrossRefPubMedGoogle Scholar
  27. 29.
    Evans EF, et al: Blood flow in muscle groups and drug absorption. Clinical Pharmacology & Therapeutics, 1975: 17: 44–47.Google Scholar
  28. 30.
    Lassen NA: Cerebral blood flow and oxygen consumption in man. Physiological Reviews, 1959: 39: 183–238.PubMedGoogle Scholar
  29. 31.
    Johnson LL, et al: Reduced left ventricular myocardial blood flow per unit mass in aortic stenosis. Circulation, 1978: 57: 582–590.PubMedGoogle Scholar
  30. 32.
    Lesser GT, Deutsch S: Measurement of adipose tissue flow and perfusion in man by uptake of 85K1. Journal of Applied Physiology, 1967: 23: 621–630.PubMedGoogle Scholar
  31. 33.
    Landis EM, Pappenheimer JR: Exchange of substances through the capillary walls. in “Handbook of Physiology”, section 2, “Circulation”, volume II, eds. Hamilton WF and Dow P, pub. American Physiological Society, Washington D.C., 1963.Google Scholar
  32. 34.
    Renkin EM: Effects of blood flow on diffusion kinetics in isolated perfused hindlegs of cats. American Journal of Physiology, 1955: 183: 125–136.PubMedGoogle Scholar
  33. 35.
    Chauvin M, et al: The influence of hepatic plasma flow on alfentanil plasma concentration plateaus achieved with an infusion model in humans: Measurement of alfentanil hepatic extraction coefficient. Anesthesia and Analgesia, 1986: 65: 999–1003.CrossRefPubMedGoogle Scholar
  34. 36.
    Stenson RE, et al: Interrelationships of hepatic blood flow, cardiac output, and blood levels of lidocaine in man. Circulation, 1971: 43: 205–211.PubMedGoogle Scholar
  35. 37.
    Nies AS, et al: Altered hepatic blood flow and drug disposition. Clinical Pharmacokinetics, 1976: 1: 135–155.CrossRefPubMedGoogle Scholar
  36. 38.
    Krejcie TC, et al: Alfentanil pharmacokinetics: Intravascular space and cardiac output. Anesthesiology, 1988: 69: A466.CrossRefGoogle Scholar
  37. 39.
    Goat VA, et al: The effect of blood flow upon the activity of gallamine triethiodide. British Journal of Anaesthesia, 1976: 48: 69–73.CrossRefPubMedGoogle Scholar
  38. 40.
    London GM, et al: Cardiopulmonary blood volume and plasma renin activity in normal and hypertensive humans. American Journal of Physiology, 1985: 249: H807–H813.PubMedGoogle Scholar
  39. 41.
    Pierson RN, et al: Extracellular water measurements:organ tracer kinetics of bromide and sucrose in rats and man. American Journal of Physiology, 1978: 235: F254–F264.PubMedGoogle Scholar
  40. 42.
    Slutsky RA, et al: Pulmonary blood volume: Analysis during exercise in patients with left ventricular dysfunction. European Journal of Nuclear Medicine, 1983: 8: 523–527.CrossRefPubMedGoogle Scholar
  41. 43.
    Maddahi J, et al: What is the normal range for left and right ventricular ejection fraction at different levels of exercise? Findings of scintgraphic ventriculography during graded ergometry in 34 normals. Journal of Nuclear Medicine, 1980: 21: P5.Google Scholar
  42. 44.
    Mangano DT, et al: The effect of increasing preload on ventricular output and ejection in man. Limitations of the Frank-Starling mechanism. Circulation, 1980: 62: 535–541.PubMedGoogle Scholar
  43. 45.
    Ross J, et al: Effects of changing heart rate in man by electrical stimulation of the right atrium. Circulation, 1965: 32: 549–558.PubMedGoogle Scholar
  44. 46.
    Firth BG, et al: Effect of increasing heart rate in patients with aortic regurgitation. Effect of incremental atrial pacing on scintigraphic, hemodynamic and thermodilution measurements. American Journal of Cardiology, 1982: 49: 1860–1867.CrossRefPubMedGoogle Scholar
  45. 47.
    Slutsky R, et al: Left ventricular size and function after subcutaneous administration of terbutaline. Assessment by cardiac pool imaging. Chest, 1981: 79: 501–505.CrossRefPubMedGoogle Scholar
  46. 48.
    Hurwitz RA, et al: Dobutamine infusion to assess ventricular function in pediatric patients. Journal of Nuclear Medicine, 1987: 28: 621.Google Scholar
  47. 49.
    Kiess MC, et al: Changes in ventricular function during emotional stress and cold exposure. Journal of Nuclear Medicine, 1984: 25: P4.Google Scholar
  48. 50.
    Barratt RL, et al: Kinetics of thiopentone in relation to the site of sampling. British Journal of Anaesthesia, 1984: 56: 1385–1391.CrossRefPubMedGoogle Scholar
  49. 51.
    Major E, et al: Influence of sample site on blood concentrations of ICI 35 868. British Journal of Anaesthesia, 1983: 55: 371–375.CrossRefPubMedGoogle Scholar
  50. 52.
    Conn HL, Goldberg J: Accuracy of a radiopotassium dilution (Stewart principle) method for the measurement of cardiac output. Journal of Applied Physiology, 1955: 7: 542–548.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1992

Authors and Affiliations

  • Gerald M. Woerlee
    • 1
  1. 1.Rijnoord HospitalAlphen aan den RijnThe Netherlands

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