The Significance of Marked “Universal” Dependence of Drug Concentration on Blood Sampling Site in Pharmacokinetics and Pharmacodynamics

  • Win L. Chiou


Until recently [1–3] it has been commonly assumed in pharmacokinetics and pharmacodynamics that “blood is blood” and blood (plasma or serum) concentrations of an endogenous or exogenous compound are practically identical, whether the blood sample is obtained from an arm artery, an arm vein, a leg vein, a pulmonary artery or a jugular vein. Such a sampling site-independent concept has apparently originated from an unrigorously tested assumption that after a bolus intravenous injection, the mixing of a substance in the entire blood circulation is extremely efficient; it was said to be complete in seconds [4, 5] or in three circulatory transit times, which is about three minutes in humans [6, 7] and much shorter in small animals [1]. The wide use of the plasma (blood) or central compartment concept in multi-compartmental or noncompartmental analysis [8–12] in the last several decades has undoubtedly contributed to the general acceptance of the above assumption.


Terminal Phase Blood Flow Rate Bolus Intravenous Injection Versus Difference Plasma Concentration Profile 
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  1. 1.
    W. L. Chiou. The phenomenon and rationale of marked dependence of drug concentration on blood sampling site. Implications in pharmacokinetics, pharmacodynamics, toxicology and therapeutics. (Parti). Clin. Pharmacokinet. 17:175–199 (1989).PubMedCrossRefGoogle Scholar
  2. 2.
    W. L. Chiou. The phenomenon and rationale of marked dependence of drug concentration on blood sampling site. Implications in pharmacokinetics, pharmacodynamics, toxicology and therapeutics. (Part II). Clin. Pharmacokinet. 17:275–290 (1989).PubMedCrossRefGoogle Scholar
  3. 3.
    T. Terada, K. Ishibashi, T. Tsuchiya, H. Noguchi, and T., Mimura. Arterial-venous concentration gradients as a potential source of error in pharmacokinetic studies. Plasma concentration differences of 6-chloro-2-pyridylmethyl nitrate on constant infusion to rats. Xenobiotica 19:661–667 (1989).PubMedCrossRefGoogle Scholar
  4. 4.
    W. L. Chiou, G. Lam, M. L. Chen, and M. G. Lee. Arterial-venous plasma concentration differences of six drugs in the dog and rabbit after intravenous administration. Res. Commun. Chem. Path. 32:27–39 (1981).Google Scholar
  5. 5.
    W. L. Chiou and G. Lam. The significance of the arterial-venous plasma concentration difference in clearance studies. Int. J. Clin. Pharm. Th. 20:197–203 (1982).Google Scholar
  6. 6.
    K. B. Bischoff. Physiological pharmacokinetics. Bull. Math. Biol. 48:309–322 (1986).PubMedGoogle Scholar
  7. 7.
    T. K. Henthron, M. J. Avram, and T. C. Krejeie. Intravascular mixing and drug distribution: The concurrent disposition of thiopental and indocyanine green. Clin. Pharmacol. Ther. 45:56–65 (1989).CrossRefGoogle Scholar
  8. 8.
    T. Teorell. Kinetics of distribution of substances administered to the body II. The intravascular modes of administration. Arch. Int. Pharmacod. T. 57:226–240 (1937).Google Scholar
  9. 9.
    A. Rescigno and G. Segre. Drugs and Tracer Kinetics, Blaisdell Publishing, New York, 1966.Google Scholar
  10. 10.
    S. Riegelman, J. C. K. Loo, and M. Rowland. Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment. J. Pharm. Sci. 57:117–123 (1968).PubMedCrossRefGoogle Scholar
  11. 11.
    M. Gibaldi and D. Perrier. Pharmacokinetics, Marcel Dekker, New York, 1982.Google Scholar
  12. 12.
    L. Z. Benet and R. L. Galeazzi. Noncompartmental determination of the steady-state volume of distribution. J. Pharm. Sci. 68:1071–1074 (1979).PubMedCrossRefGoogle Scholar
  13. 13.
    G. T. Tucker and L. E. Mather. Pharmacokinetics of local anesthetic agents. Brit. J. Anaesth. 47:213–244 (1975).PubMedGoogle Scholar
  14. 14.
    G. T. Tucker and L. E. Mather. Clinical pharmacokinetics of local anesthetics. Clin. Pharmacokinet. 4:241–278 (1979).PubMedCrossRefGoogle Scholar
  15. 15.
    R. B. Forney, F. W. Hughes, R. N. Harger, and A. B. Richards. Alcohol distribution in the vascular system: Concentration of orally administered alcohol in blood from various points in the vascular system, and in rebreathed air during absorption. Quart. J. Stud. Alcohol. 25:205–220 (1954).Google Scholar
  16. 16.
    S. Bojolm, O. B. Paulson, and H. Flachs. Arterial and venous concentrations of phenobarbital, phenytoin, clonazepam, and diazepam after rapid intravenous injections. Clin. Pharmacol. Ther. 32:478–483 (1982).CrossRefGoogle Scholar
  17. 17.
    F. J. Baud, P. Houze, C. Bismuth, A. Jaeger and C. Keyes. Toxicokinetics of paraquate through the heart-lung block. Six cases of acute human poisoning. J. Toxicol. Clin. Toxi. 26:35–50 (1988).CrossRefGoogle Scholar
  18. 18.
    G. Lam and W. L. Chiou. Arterial and venous blood sampling in pharmacokinetic studies: Propranolol in rabbits and dogs. Res. Commun. Chem. Path. 33:33–48 (1981).Google Scholar
  19. 19.
    Y. M. Amin, E. B. Thompson, and W. L. Chiou. Fluorocarbon aerosol propellants XII: Correlation of blood levels of trichloromonofluoromethane to cardiovascular and respiratory responses in anesthetized dogs. J. Pharm. Sci. 68:160–163 (1979).PubMedCrossRefGoogle Scholar
  20. 20.
    W. L. Chiou. A new model-independent physiological approach to study hepatic drug clearance and its applications. Int. J. Clin. Pharm. Th. 22:577–590 (1984).Google Scholar
  21. 21.
    W. L. Chiou. The effect of change in luminal perfusion rate on intestinal drug absorption studied by a simple unified organ clearance approach. Pharmaceut. Res. 6:1056–1059 (1989).CrossRefGoogle Scholar
  22. 22.
    W. L. Chiou and H. J. Lee. Effect of change in blood flow on hemodialysis clearance studied by a simple unified organ clearance approach. Res. Commun. Chem. Path. 65:393–396 (1989).Google Scholar
  23. 23.
    A. C. Guyton. Textbook of Medical Physiology, 7th ed., W. B. Saunders, Philadelphia, 1986.Google Scholar
  24. 24.
    P. S. Randhawa. Theophylline blood levels in circulatory shock. Ann. Intern. Med. 110:1035 (1989).PubMedCrossRefGoogle Scholar
  25. 25.
    J. M. Collins and R. L Dedrick. Contribution of lungs to total body clearance: Linear and nonlinear effects. J. Pharm. Sci. 71:66–70 (1982).PubMedCrossRefGoogle Scholar
  26. 26.
    W. L. Chiou. Potential pitfalls in the conventional pharmacokinetic studies: Effects of the initial mixing of drug in blood and the pulmonary first-pass elimination. J. Pharmacokin. Biopharm. 7:527–536 (1979).CrossRefGoogle Scholar
  27. 27.
    M. L. Chen and W. L. Chiou. Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate in rabbits after intravenous administration. J. Pharmacokin. Biopharm. 11:499–513 (1983).CrossRefGoogle Scholar
  28. 28.
    H. L. Fung. Pharmacokinetics of nitroglycerin and long-acting nitrate esters. Am. J. Med. 74:13–20 (1983).PubMedCrossRefGoogle Scholar
  29. 29.
    A. B. Hill, C. J. Bowley, M. L. Nahrwold, P. R. Knight, M. M. Kirsh, and J. K. Denlinger. Intranasal administration of nitroglycerin. Anesthesiology 54:346–348 (1981).PubMedCrossRefGoogle Scholar
  30. 30.
    W. L. Chiou, G. Lam, M. L. Chen, and M. G. Lee. Effect of arterial-venous plasma concentration differences on the determination of mean residence time of drugs in the body. Res. Commun. Chem. Path. 35:17–26 (1982).Google Scholar
  31. 31.
    R. Haekel. Relationship between intraindividual variation of the saliva/plasma and of the arteriovenous concentration ratio as demonstrated by the administration of caffeine. J. Clin. Chem. Clin. Bio. 28:279–284 (1990).Google Scholar
  32. 32.
    W. L. Chiou, G. Lam, M. L. Chen, and M. G. Lee. Instantaneous input hypothesis in pharmacokinetic studies. J. Pharm. Sci. 70:1037–1039 (1981).PubMedCrossRefGoogle Scholar
  33. 33.
    M. L. Chen, G. Lam, M. G. Lee, and W. L. Chiou. Arterial and venous blood sampling in pharmacokinetic studies: Griseofulvin. J. Pharm. Sci. 71:1386–1389 (1982).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Win L. Chiou
    • 1
  1. 1.Department of PharmacodynamicsThe University of Illinois at ChicagoUSA

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