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Predicting the Onset of Nonlinear Pharmacokinetics

Stein, Andrew and Peletier, Lambertus (2018) Predicting the Onset of Nonlinear Pharmacokinetics. CPT: Pharmacometrics and Systems Pharmacology, 7 (10). pp. 670-677. ISSN 21638306


When analyzing the pharmacokinetics (PK) of drugs, one is often faced with concentration C vs. time curves, which display a sharp transition at a critical concentration Ccrit. For C > Ccrit, the curve displays linear clearance and for C < Ccrit clearance increases in a nonlinear manner as C decreases. Often, it is important to choose a high enough dose such that PK remains linear in order to help ensure that continuous target engagement is achieved throughout the duration of therapy. In this article, we derive a simple expression for Ccrit for models involving linear and nonlinear (saturable) clearance, such as Michaelis-Menten and target-mediated drug disposition (TMDD) models. Study Highlights.

Item Type: Article
Date Deposited: 11 Dec 2018 00:45
Last Modified: 11 Dec 2018 00:45


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