Abstract.
The direct pharmacological effect E is described by the E max model relating E to the drug plasma concentration C p . The area under the effect vs. time curve (AUC E ) is used as the measurement of the total net pharmacological effect. The drug plasma concentrations are solutions of compartmental systems of ordinary differential equations with the input terminated after a finite time and controlled in a proportional manner by a single dose-like parameter. The asymptotics of the time derivative of C p for large doses are derived and used as conditions which have to be satisfied by functions for which the asymptotics of the integral defining AUC E are derived. The AUC E is proportional to the time T C>EC50 for which the drug concentration stays above the threshold level EC 50. The threshold EC 50 denotes the drug plasma concentration which elicits 50% of the maximum effect. The parameter T C>EC50 is proportional to the logarithm of drug dose for large doses and its asymptotics is calculated up to the order o(1) as dose increases to infinity. The results are applied to basic pharmacokinetic systems.
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Received: 7 December 1999 / Revised version: 23 May 2000 / Published online: 23 October 2000
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Krzyzanski, W. Asymptotics of the total net direct pharmacological effect for large drug doses. J Math Biol 41, 477–492 (2000). https://doi.org/10.1007/s002850000052
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DOI: https://doi.org/10.1007/s002850000052