Mixed-Order Kinetics (Nonlinear Kinetics)

Mixed-Order Kinetics (Nonlinear Kinetics)

In some instances, the kinetics of a pharmacokinetic process changes from predominantly first-order to predominantly zero-order with increasing dose or chronic medication. A mixture of both first-order and zero-order kinetics is observed in such cases and therefore the process is said to follow mixed-order kinetics. Since deviations from an originally linear pharmacokinetic profile are observed, the rate process of such a drug is called as nonlinear kinetics. Mixed order kinetics is also termed as dose-dependent kinetics as it is observed at increased or multiple doses of some drugs. Nonlinearities in pharmacokinetics have been observed in –

^·            Drug absorption (e.g. vitamin C)

^·            Drug distribution (e.g. naproxen), and

^·            Drug elimination (e.g. riboflavin).

The phenomena is seen when a particular pharmacokinetic process involves presence of carriers or enzymes which are substrate specific and have definite capacities and can get saturated at high drug concentrations (i.e. capacity-limited). The kinetics of such capacity-limited processes can be described by the Michaelis-Menten kinetics.