Nonlinear Pharmacokinetics

| Home | | Biopharmaceutics and Pharmacokinetics |

Chapter: Biopharmaceutics and Pharmacokinetics : Nonlinear Pharmacokinetics

In most cases, at therapeutic doses, the change in the amount of drug in the body or the change in its plasma concentration due to absorption, distribution, binding, metabolism or excretion, is proportional to its dose, whether administered as a single dose or as multiple doses.


Nonlinear Pharmacokinetics

In most cases, at therapeutic doses, the change in the amount of drug in the body or the change in its plasma concentration due to absorption, distribution, binding, metabolism or excretion, is proportional to its dose, whether administered as a single dose or as multiple doses. In such situations, the rate processes are said to follow first-order or linear kinetics and all semilog plots of C versus t for different doses, when corrected for dose administered, are superimposable. This is called as principle of superposition. The important pharmacokinetic parameters viz. F, Ka, KE, Vd, ClR and ClH which describe the time-course of a drug in the body remain unaffected by the dose i.e. the pharmacokinetics is dose-independent.

In some instances, the rate process of a drug’s ADME are dependent upon carrier or enzymes that are substrate-specific, have definite capacities, and susceptible to saturation at high drug concentration. In such cases, an essentially first-order kinetics transform into a mixture of first-order and zero-order rate processes and the pharmacokinetic parameters change with the size of the administered dose. The pharmacokinetics of such drugs are said to be dose-dependent. Other terms synonymous with it are mixed-order, nonlinear and capacity-limited kinetics. Drugs exhibiting such a kinetic profile are sources of variability in pharmacological response.

There are several tests to detect nonlinearity in pharmacokinetics but the simplest ones are –

1. Determination of steady-state plasma concentration at different doses. If the steady-state concentrations are directly proportional to the dose, then linearity in the kinetics exists. Such proportionality is not observable when there is nonlinearity.

2. Determination of some of the important pharmacokinetic parameters such as fraction bioavailable, elimination half-life or total systemic clearance at different doses of the drug. Any change in these parameters which are usually constant, is indicative of nonlinearity.

Contact Us, Privacy Policy, Terms and Compliant, DMCA Policy and Compliant

TH 2019 - 2023 pharmacy180.com; Developed by Therithal info.