Skip to main content

Pharmacokinetics of morphine in plasma and discrete areas of the rat brain

Journal of Pharmacokinetics and Biopharmaceutics volume 3, pages 293–302 (1975)Cite this article

Abstract

After intravenous administration of an analgesic dose of morphine into rat, the time course of morphine concentrations was followed in plasma, whole brain, and four discrete areas of the brain during 8 hr. These concentration curves indicated a three-exponential function which could be described by a mammillary system of three compartments. Maximal brain levels were obtained 15–20 min after injection, showing a fairly even distribution pattern of morphine. The plasma to whole brain ratio showed three-exponential characteristics, approaching a constant value of about 4.7–4.8 after 4 hr. By use of the SAAM-25 program, the experimental data from plasma and brain were simultaneously fitted to five separate sets of three-compartment models. Results obtained implied the uniqueness of the computed transfer constants of the three-compartment model.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. S. J. Mulé.Physiological disposition of narcotic agonists and antagonists. in D. H. Clouet (ed.),Narcotic Drugs, Biochemical Pharmacology, Plenum Press. New York, 1971, pp. 99–121.

    Chapter  Google Scholar 

  2. L. Paalzow and G. Paalzow. Studies on the relationship between morphine analgesia and the brain catecholamines in mice.Acta Pharmacol. Toxicol. 30:104–114 (1971).

    CAS  Article  Google Scholar 

  3. L. Paalzow and G. Paalzow. Blood and brain concentration of morphine in relation to the analgesic activity in mice.Acta Pharm. Suecica 8:329–336 (1971).

    CAS  Google Scholar 

  4. L. Paalzow. Studies on the relationship between the analgesic activity of salicylic acid and the brain catecholamines in mice.Acta Pharmacol. Toxicol. 32:11–21 (1973).

    CAS  Article  Google Scholar 

  5. G. Paalzow, L. Paalzow, and B. Stalby. Pentazocine analgesia and regional rat brain catecholamines.Eur. J. Pharmacol. 27:78–88 (1974).

    CAS  PubMed  Article  Google Scholar 

  6. B. Dahlström and L. Paalzow. Quantitative determination of morphine by gas-liquid chromatography and electron-capture detection.J. Pharm. Pharmacol. 27:172–176 (1975).

    PubMed  Article  Google Scholar 

  7. J. Glowinski and L. L. Iversen. Regional studies of catecholamines in the rat brain. I.J. Neurochem. 13:655–669 (1966).

    CAS  PubMed  Article  Google Scholar 

  8. B. Dahlström, G. Paalzow, and L. Paalzow. Pharmacokinetical evaluation of morphine analgesia in the rat.Proc. Sec. Int. Congr. Pharmacol. Budapest (1974).

  9. A. Rescigno and G. Segre. The precursor-product relationship.J. Theoret. Biol. 1:498 (1961).

    CAS  Google Scholar 

  10. A. Rescigno and G. Segre. In A. Rescigno and G. Segre (eds.),Drug and Tracer Kinetics, Blaisdell, Waltham, Mass., 1966.

    Google Scholar 

  11. S. Spector and E. S. Vesell. Disposition of morphine in man.Science 174:421–422 (1971).

    CAS  PubMed  Article  Google Scholar 

  12. S. Spector. Quantitative determination of morphine in serum by radioimmunoassay.J. Pharmacol. Exp. Ther. 178:253–258 (1971).

    CAS  PubMed  Google Scholar 

  13. B. A. Berkowitz, K. V. Cerreta, and S. Spector. The influence of physiologic and pharmacologie factors on the disposition of morphine as determined by radioimmunoassay.J. Pharmacol. Exp. Ther. 191:527–534 (1974).

    CAS  PubMed  Google Scholar 

  14. M. Berman. Compartmental analysis in kinetics. In R. W. Stacy and B. D. Waxman (eds.),Computers in Biomedical Research II, Academic Press, London. 1965, pp. 173–201.

    Google Scholar 

  15. A. E. Takemori and M. W. Stenwick. Studies on the uptake of morphine by the choroid plexusin vitro.J. Pharmacol. Exp. Ther. 154:586–594 (1966).

    CAS  PubMed  Google Scholar 

  16. C. C. Hug, Jr. Transport of narcotic analgesics by choroid plexus and kidney tissuein vitro.Biochem. Pharmacol. 16:345–359 (1967).

    CAS  PubMed  Article  Google Scholar 

  17. J. H. Wang and A. E. Takemori. Studies on the transport of morphine into the cerebrospinal fluid of rabbits.J. Pharmacol. Exp. Ther. 183:41–48 (1972).

    CAS  PubMed  Google Scholar 

  18. A. Herz and H.-J. Teschemacher. Activities and sites of antinociceptive action of morphinelike analgesics. In N. J. Harper and A. B. Simmonds (eds.),Advances in Drug Research, Vol. 6, Academic Press, London, 1971, pp. 79–121.

    Google Scholar 

  19. S. J. Mulé, L. A. Woods, and L. B. Mellett. Distribution of N-C14-methyl labelled morphine. II. Effect of nalorphine in the central nervous system of nontolerant dogs and observations on metabolism.J. Pharmacol. 136:242–249 (1962).

    Google Scholar 

  20. J. Jóhannesson and L. A. Woods. Analgesic action and brain and plasma levels of morphine and codeine in morphine tolerant, codeine tolerant and non-tolerant rats.Acta Pharmacol. Toxicol. 21:381–396 (1964).

    Article  Google Scholar 

  21. E. Leong Way. Pharmacologie implications of some factors influencing brain uptake of morphine.Arch. Biol. Med. Exp. 4:92–104 (1967).

    Google Scholar 

  22. J. W. Miller and H. W. Elliott. Rat tissue levels of carbon-14 labelled analgesics as related to pharmacological activity.J. Pharmacol. Exp. Ther. 113:283–291 (1955).

    CAS  PubMed  Google Scholar 

  23. S. J. Mulé and L. A. Woods. Distribution ofN-C 14-methyl labelled morphine. I. In central nervous system of non-tolerant and tolerant dogs.J. Pharmacol. Exp. Ther. 136:232–241 (1962).

    PubMed  Google Scholar 

  24. P. Schubert, H. Teschemacher, G. W. Kreutzberg, and A. Herz. Intracerebral distribution pattern of radioactive morphine and morphine-like drugs after intraventricular and intrathecal injection.Histochemie 22:277–288 (1970).

    CAS  Article  Google Scholar 

  25. L.-E. Appelgren and L. Terenius. Differences in the autoradiographic localization of labelled morphine-like analgesics in the mouse.Acta Physiol. Scand. 88:175–182 (1973).

    CAS  PubMed  Article  Google Scholar 

  26. G. Levy, M. Gibaldi, and W. J. Jusko. Multicompartment pharmacokinetic models and pharmacologie effects.J. Pharm. Sci. 58:422–424 (1969).

    CAS  PubMed  Article  Google Scholar 

  27. M. Gibaldi, G. Levy, and H. Weintraub. Drug distribution and pharmacologie effects.Clin. Pharmacol. Ther. 12:734–742 (1971).

    CAS  PubMed  Google Scholar 

  28. J. G. Wagner. Kinetics of the pharmacologie response. I.J. Theoret. Biol. 20:173–201 (1968).

    CAS  Article  Google Scholar 

  29. J. G. Wagner. Relations between drug concentration and response.J. Mond. Pharm. 14: 279–310 (1971).

    Google Scholar 

  30. M. Rowland. Application of clearance concepts to some literature data on drug metabolism in the isolated perfused lever preparation andin vivo.Eur. J. Pharmacol. 17:352–356 (1972).

    CAS  PubMed  Article  Google Scholar 

  31. M. Berman, M. F. Weiss, and E. Shahn. Some formal approaches to the analysis of kinetic data in terms of linear compartmental systems.Biophys. J. 2:289–316 (1962).

    CAS  PubMed Central  PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Pharmacology, Pharmaceutical Faculty, Biomedical Center, University of Uppsala, Box 573, S-751 23, Uppsala, Sweden

    Bengt E. Dahlström & Lennart K. Paalzow

  2. Centrallaboratoriet, Apoteksbolaget AB, Box 3045, S-171 03, Solna 3, Sweden

    Bengt E. Dahlström & Lennart K. Paalzow

Authors
  1. Bengt E. Dahlström
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lennart K. Paalzow
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Dahlström, B.E., Paalzow, L.K. Pharmacokinetics of morphine in plasma and discrete areas of the rat brain. Journal of Pharmacokinetics and Biopharmaceutics 3, 293–302 (1975). https://doi.org/10.1007/BF01082303

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01082303

Key words

  • morphine
  • pharmacokinetics
  • pharmacokinetic models