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A new method to estimate parameters of pharmacokinetics with enterohepatic circulation

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Summary

A new method of estimating pharmacokinetic parameters for enterohepatic recirculation models is presented. The algorithm, based on the simplex method, assures a convergence toward theminimum minimorum; provides reliable parameters, even in large numbers; and handles up to five cycle effects in five established models: IV, EV, mono-, bi- or tricompartmental. For each model, the reabsorption rate may be considered to be slow (characterised by a rate constant with a significant value) or instantaneous (an infinite rate constant).

Two examples are given to illustrate the qualities of the software that incorporates this new algorithm. The first relates to the pharmacokinetics of zinc orally given to humans; the second treats the kinetics of α-methylDOPA given to dogs intra-arterially (note: values of plasma concentrations have been extracted from the literature).

The importance of the choice of the weighting is emphasised.

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References

  1. Abi Khalil F., Dubois J., Hanocq M., Atassi G. (1986): A new algorithm for computing the parameters of linear compartment models in pharmacokinetics. Eur. J. Drug Metab. Pharmacokinet., 11, 51–59.

    Article  CAS  Google Scholar 

  2. Dubois J., Atassi G., Hanocq M., Abi Khalil F. (1986): Pharmacokinetics and metabolism of hexamethylmelamine in mice after IP administration. Cancer Chemother. Pharmacol., 18, 226–230.

    Article  CAS  PubMed  Google Scholar 

  3. Dubois J., Atassi G., Hanocq M., Abi Khalil F. (1988): Pharmacokinetics and metabolism of hexamethylmelamine in mice bearing RC tumor. Cancer Chemother. Pharmacol., 22, 282–288.

    Article  CAS  PubMed  Google Scholar 

  4. Dubois J., Atassi G., Hanocq M., Abi Khalil F. (1989): Tumor pharmacokinetics of hexamethylmelamine in CDF1 mice bearing P 388 leukemia. Anticancer Res., 9, 255–260.

    CAS  PubMed  Google Scholar 

  5. Dubois J. (1989): Contribution à la compréhension de méthodologies pharmacocinétiques et de mise en évidence de cytotoxicité de certains dérivés anticancéreux. Thèse de doctorat, Institut de Pharmacie, Univeristé Libre de Bruxelles.

  6. Metzler C.M., Elfring G.L., McEwen A.J. (1974): A package of computer programs for pharmacokinetic modelling. Biometrics, 2, 562–570.

    Google Scholar 

  7. Kochak G.M., Mason N.D. (1985): The pharmacokinetics of α-methyldopa in dogs. J. Pharmacokinet. Biopharmacol., 13, 405–423.

    Article  CAS  Google Scholar 

  8. Akaike H. (1974): A new look at the statistical model identification, IEE. Trans. Autom. Contr., AC19, 716–789.

    Article  Google Scholar 

  9. Imbimbo B.P., Imbimbo E., Dainott S., Verotta D., Bassotti G. (1988): A new criterion for selection of pharmacokinetic multiex ponential equations. J. Pharm. Sci., 77, 784–789.

    Article  CAS  PubMed  Google Scholar 

  10. Schwarz G. (1978): Estimating the dimensions of a model. Ann. Stat., 6, 461–464.

    Article  Google Scholar 

  11. Edwards A.W.F. (1972): Likelihood. An account of the statistical concept of likelihood and its application to scientific interference. Cambridge: Cambridge University Press.

    Google Scholar 

  12. Neve J., Hanocq M., Peretz A., Famaey J.P., Abi Khalil F. (1991): Pharmacokinetic study of orally administered zinc in humans: evidence for an enteral recirculation. Eur. J. Drug Metab. Pharmacokinet., 16, 315–323.

    Article  CAS  PubMed  Google Scholar 

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Abi Khalil, F., Hanocq, M. & Dubois, J. A new method to estimate parameters of pharmacokinetics with enterohepatic circulation. Eur. J. Drug Metab. Pharmacokinet. 18, 131–139 (1993). https://doi.org/10.1007/BF03188787

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  • DOI: https://doi.org/10.1007/BF03188787

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