Skip to main content
SpringerLink
Log in

A Recirculatory Model of the Pulmonary Uptake and Pharmacokinetics of Lidocaine Based on Analysis of Arterial and Mixed Venous Data from Dogs

  • Published:
Journal of Pharmacokinetics and Biopharmaceutics Aims and scope Submit manuscript

Abstract

Pulmonary uptake of basic amine xenobiotics such as lidocaine may influence the onset of drug effect and ameliorate toxicity. To date, pharmacokinetic analysis of pulmonary drug uptake has been only semiquantitative and ill-suited for relating pharmacodynamics to pharmacokinetics or jar estimating the time course of the fraction of drug dose residing in the lung during a single pass. We have developed recirculatory models in an experiment in which lidocaine was injected into the right atrium simultaneously with markers of intravascular space (indocyanine green) and total body water (antipyrine): this was followed by rapid arterial and mixed venous blood sampling. Such models are interpretable physiologically and are capable of characterizing the kinetics of the pulmonary uptake of lidocaine in addition to peripheral tissue distribution and elimination. The apparent pulmonary tissue volume of lidocaine (39 ml/kg) was nearly ninefold greater than that of antipyrine (4.5 ml/kg). The recirculatory model characterized both arterial and mixed venous data, but the latter data were not essential for estimating lidocaine's pulmonary disposition either before or after recirculation of drug was evident.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. C. Post. Studies on the pharmacokinetic function of the lung with special reference to lidocaine. Acta Pharmacol. Toxicol. 44(Suppl. 1):1–53 (1979).

    Google Scholar 

  2. R. E. Howell and P. N. Lanken. Pulmonary accumulation of propranolol in vivo: Sites and physiochemical mechanism. J. Pharmacol. Exp. Ther. 263:130–135 (1992).

    CAS  PubMed  Google Scholar 

  3. D. L. Roerig, K. J. Kotrly, E. J. Vucins, S. B. Ahlf, C. A. Dawson, and J. P. Kampine. First pass uptake of fentanyl, meperidine, and morphine in the human lung. Anesthesiology 67:466–472 (1987).

    Article  CAS  PubMed  Google Scholar 

  4. P. M. Bokesch, A. R. Castaneda, G. Ziemer, and J. M. Wilson. The influence of a right-to-left cardiac shunt on lidocaine pharmacokinetics. Anesthesiology 67:739–744 (1987).

    Article  CAS  PubMed  Google Scholar 

  5. C. Post, R. G. Andersson, A. Ryrfeldt, and E. Nilsson. Transport and binding of lidocaine by lung slices and perfused lung of rats. Acta Pharmacol. Toxicol. 43:156–163 (1978).

    Article  CAS  Google Scholar 

  6. K. Taeger, E. Weninger, F. Schmelzer, M. Adt, N. Franke, and K. Peter. Pulmonary kinetics of fentanyl and alfentanil in surgical patients. Br. J. Anaesth. 61:425–434 (1988).

    Article  CAS  PubMed  Google Scholar 

  7. 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).

    Article  CAS  Google Scholar 

  8. T. C. Krejcie, T. K. Henthorn, C. A. Shanks, and M. J. Avram. A recirculatory pharmacokinetic model describing the circulatory mixing, tissue distribution and elimination of antipyrine in dogs. J. Pharmacol. Exp. Ther. 269:609–616 (1994).

    CAS  PubMed  Google Scholar 

  9. Y. F. Huang, R. N. Upton, L. E. Mather, and W. B. Runciman. An assessment of methods for sampling blood to characterize rapidly changing blood drug concentrations. J. Pharm. Sci. 80:847–851 (1991).

    Article  CAS  PubMed  Google Scholar 

  10. D. M. Grasela, M. L. Rocci, Jr, and P. H. Vlasses. Experimental impact of assay-dependent differences in plasma indocyanine green concentration determinations. J. Pharmacokin. Biopharm. 15:601–613 (1987).

    Article  CAS  Google Scholar 

  11. T. K. Henthorn, M. J. Avram, T. C. Krejcie, C. A. Shanks, A. Asada, and D. A. Kaczynski. Minimal compartmental model of circulatory mixing of indocyanine green. Am. J. Physiol. 262:H903–H910 (1992).

    CAS  PubMed  Google Scholar 

  12. K. Ahmad and F. Medzihradsky. Distribution of lidocaine in blood and tissue after single doses and steady infusion. Res. Commun. Chem. Pathol. Pharmacol. 2:813–828 (1971).

    CAS  PubMed  Google Scholar 

  13. T. C. Krejcie, J. A. Jacquez, M. J. Avram, C. U. Niemann, C. A. Shanks, and T. K. Henthorn. Use of parallel Erlang density functions to analyze first-pass pulmonary uptake of multiple indicators in dogs. J. Pharmacokin. Biopharm. 24:569–588 (1996).

    Article  CAS  Google Scholar 

  14. K. L. Zierler. In W. F. Hamilton (ed.), Handbook of Physiology, Section 2, Circulation. Vol. 1. American Physiological Society, Washington, DC. 1962, pp. 585–615.

    Google Scholar 

  15. Y. W. Zhen, S. E. Cross, and M. S. Roberts. Influence of physicochemical parameters and perfusate flow rate on the distribution of solutes in the isolated perfused rat hindlimb determined by the impulse-response technique. J. Pharm. Sci. 84:1020–1027 (1995).

    Article  Google Scholar 

  16. B. S. Berman, E. Shahn, and M. J. Weiss. The routine fitting of kinetic data to models: A mathematical formalism for digital computers. Biophys. J. 2:275–287 (1962).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. S. Siegel. Nonparametric Statistics for the Behavioral Sciences, McGraw-Hill, New York, 1956.

    Google Scholar 

  18. P. Caldini, S. Permutt, J. A. Waddell, and R. L. Riley. Effect of epinephrine on pressure, flow, and volume relationships in the systemic circulation of dogs. Circ. Res. 34:606–623 (1974).

    Article  CAS  PubMed  Google Scholar 

  19. K. L. Brigham, L. H. Ramsey, J. D. Snell, and C. R. Merritt, III. On defining the pulmonary extravascular water volume. Circ. Res. 29:385–397 (1971).

    Article  CAS  PubMed  Google Scholar 

  20. R. M. Effros, G. R. Mason, E. Reid, L. Graham, and P. Silverman. Diffusion of labeled water and lipophilic solutes in the lung. Microvasc. Res. 29:45–55 (1985).

    Article  CAS  PubMed  Google Scholar 

  21. C. M. Metzler. In M. Rowland and G. T. Tucker (eds.), international Encyclopedia of Pharmacology and Therapeutics. Section 122, Pharmacokinetics: Theory and Methodology, Pergamon, New York, 1986, pp. 407–420.

    Google Scholar 

  22. W. O. Cua, G. Basset, F. Bouchonnet, R. A. Garrick, G. Saumon, and F. P. Chinard. Endothelial and epithelial permeabilities to antipyrine in rat and dog lungs. Am. J. Physiol. 258:H1321–H1333 (1990).

    CAS  PubMed  Google Scholar 

  23. L. Jorfeldt, D. H. Lewis, J. B. Lofstrom, and C. Post. Lung uptake of lidocaine in healthy volunteers. Acta Anaesth. Scand. 23:567–574 (1979).

    Article  CAS  PubMed  Google Scholar 

  24. 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 I). [Review]. Clin. Pharmacokin. 17:175–199 (1989).

    Article  CAS  Google Scholar 

  25. 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). [Review]. Clin. Pharmacokin. 17:275–290 (1989).

    Article  CAS  Google Scholar 

  26. G. Clausen, A. Hope, and K. Aukland. Partition of 125I-iodoantipyrine among erythrocytes, plasma, and renal cortex in the dog. Acta Physiol. Scand. 107:63–68 (1979).

    Article  CAS  PubMed  Google Scholar 

  27. C. A. Dawson, C. W. Christensen, D. A. Rickaby, J. H. Linehan, and M. R. Johnston. Lung damage and pulmonary uptake of serotonin in intact dogs. J. Appl. Physiol. 58:1761–1766 (1985).

    CAS  PubMed  Google Scholar 

  28. N. Benowitz, R. P. Forsyth, K. L. Melmon, and M. Rowland. Lidocaine disposition kinetics in monkey and man. II. Effects of hemorrhage and sympathomimetic drug administration. Clin. Pharmacol. Ther. 16:99–109 (1974).

    CAS  PubMed  Google Scholar 

  29. K. Tanaka, Y. Oda, A. Asada, M. Fujimori, and Y. Funae. Metabolism of lidocaine by rat pulmonary cytochrome P450. Biochem. Pharmacol. 47:1061–1066 (1994).

    Article  CAS  PubMed  Google Scholar 

  30. D. L. Roerig, R. R. Dahl, C. A. Dawson, and R. I. Wang. Effect of plasma protein binding on the uptake of methadone and diazepam in the isolated perfused rat lung. Drug Metab. Dispos. 12:536–542 (1984).

    CAS  PubMed  Google Scholar 

  31. G. S. Sedek, T. I. Ruo, M. C. Frederiksen, J. W. Frederiksen, S. R. Shih, and A. J. Atkinson, Jr. Splanchnic tissues are a major part of the rapid distribution spaces of inulin, urea and theophylline. J. Pharmacol. Exp. Ther. 251:1026–1031 (1989).

    CAS  PubMed  Google Scholar 

  32. D. R. Wada and D. S. Ward. The hybrid model: A new pharmacokinetic model for computer-controlled infusion pumps. IEEE Trans. Biomed. Eng. 41:134–142 (1994).

    Article  CAS  PubMed  Google Scholar 

  33. E. M. Renkin. Effects of blood flow on diffusion kinetics in isolated perfused hindlegs of cats. Am. J. Physiol. 183:125–136 (1955).

    CAS  PubMed  Google Scholar 

  34. S. Bjorkman, D. R. Wada, D. R. Stanski, and W. F. Ebling. Comparative physiological pharmacokinetics of fentanyl and alfentanil in rats and humans based on parametric single-tissue models. J. Pharmacokin. Biopharm. 22:381–410 (1994).

    Article  CAS  Google Scholar 

  35. W. F. Ebling, D. R. Wada, and D. R. Stanski. From piecewise to full physiologic pharmacokinetic modeling: applied to thiopental disposition in the rat. J. Pharmacokin. Biopharm. 22:259–292 (1994).

    Article  CAS  Google Scholar 

  36. T. G. Coleman, R. D. Manning, Jr, R. A. Norman, Jr, and A. C. Guyton. Dynamics of water isotope distribution. Am. J. Physiol. 223:1371–1375 (1972).

    CAS  PubMed  Google Scholar 

  37. A. Rescigno and J. S. Beck. The use and abuse of models. J. Pharmacokin. Biopharm. 15:327–344 (1987).

    Article  CAS  Google Scholar 

  38. T. C. Krejcie, T. K. Henthorn, C. U. Niemann, C. Klein, D. K. Gupta, W. B. Gentry, C. A. Shanks, and M. J. Avram. Recirculatory pharmacokinetic models of markers of blood, extracellular fluid, and total body water administered concomitantly. J. Pharmacol. Exp. Ther. 278:1051–1057 (1996).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Northwestern University Medical School, CH—WI39, 303 E. Chicago Avenue, Chicago, Illinois, 60611 3008

    Tom C. Krejcie, Michael J. Avram, W. Brooks Gentry, Claus U. Niemann, Mary P. Janowski & Thomas K. Henthorn

Authors
  1. Tom C. Krejcie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael J. Avram
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Brooks Gentry
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claus U. Niemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mary P. Janowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Thomas K. Henthorn
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krejcie, T.C., Avram, M.J., Brooks Gentry, W. et al. A Recirculatory Model of the Pulmonary Uptake and Pharmacokinetics of Lidocaine Based on Analysis of Arterial and Mixed Venous Data from Dogs. J Pharmacokinet Pharmacodyn 25, 169–190 (1997). https://doi.org/10.1023/A:1025780012960

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1025780012960

Search

Navigation