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If a drug follows linear pharmacokinetics, Css or AUC increases proportionally with dose resulting in a straight line on the plot. Nonlinear pharmacokinetics occurs when the Css or AUC versus dose plot results in something other than a straight line. If a drug follows Michaelis-Menten pharmacokinetics (eg phenytoin, aspirin), as steady-state drug concentrations approach Km, serum concentrations increase more than expected due to dose increases. If a drug follows nonlinear protein binding (eg, valproic acid, disopyramide) or autoinduction (eg, carbamazepine), total steady-state drug concentrations increase less than expected as dose increases. Source: Valproic Acid, Applied Clinical Pharmacokinetics, 3e Citation: Bauer LA. Applied Clinical Pharmacokinetics, 3e; 2015 Available at: http://mhmedical.com/ Accessed: May 12, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved
