Drug Distribution as One-Compartment Model and Elimination by Nonlinear Pharmacokinetics: Overview

Drug administration through various routes results in mixed drug elimination, involving both nonlinear and linear processes.

The metabolism of drugs yields different metabolites through parallel pathways. At low doses, metabolite formation follows first-order kinetics, but at higher doses, the metabolizing enzyme saturation induces nonlinear metabolite formation.

This elimination equation combines first-order and Michaelis-Menten kinetics. The first-order rate constant,  k,  represents the sum of all first-order elimination processes, and the second term of the equation signifies the saturable process.

For instance, niacin, undergoing extensive first-pass metabolism, exemplifies dosing rate specificity.

One metabolic pathway involves glycine conjugating to nicotinic acid to form nicotinuric acid.

Another one results in the formation of nicotinamide adenine dinucleotide, which is further metabolized into several metabolites. 

Administering multiple doses of niacin extended-release tablets to treat hyperlipidemia results in saturation of these metabolic pathways, establishing a nonlinear relationship between the niacin dose and plasma drug concentration.