Structural identifiability of “first-pass” models
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This paper considers the structural identifiability of two compartmental models classically used to describe the pharmacokinetics of drugs orally administered and transformed into a metabolite with a firstpass effect at the hepatic level. The simplest model proves not to be globally identifiable even when plasma and urinary measurements of the drug and metabolite concentrations are made. It admits two sets of admissible solutions, so that a prioriknowledge must be introduced to distinguish them. The more complex model appears globally identifiable when blood and urine measurements are made.
Key wordsFirst-pass effect structural identifiability compartmental models
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- 6.L. Balant and E. R. Garrett. Computer use in pharmacokinetics. In E. R. Garret and J. L. Hirtz (eds.),Drug and Fate Metabolism, Vol. 4, Dekker, New York, 1983, pp. 59–66.Google Scholar
- 8.L. Chauvelot, A. Venot, and E. Walter. Pharmacocinétique humaine de la glafénine et de son principal métabolite. InProceedings of the Second European Congress of Biopharmaceutics and Pharmacokinetics, Salamanca, 1984, Vol. 2, pp. 591–599.Google Scholar
- 10.E. Walter. Identifiability of state space models.Lecture Notes in Biomathematics, Vol. 46, Springer-Verlag, Berlin, 1982.Google Scholar
- 11.K. R. Godfrey.Compartmental Models and Their Application, Academic Press, London, 1983.Google Scholar
- 12.D. H. Anderson. Compartmental modeling and tracer kinetics.Lecture Notes in Biomathematics, Vol. 50, Springer-Verlag, Berlin, 1983.Google Scholar
- 14.M. Milanese and G. Belforte. Structural problems in identification, state estimation and aggregation.Large Scale Systems 2:97–104 (1981).Google Scholar