Pharmacokinetics

Pharmacokinetics is a new science that started to gain prominence in the late 1950'borrowing many of its concepts from the engineering field and with a significant emphasis on mathematics. Now, however, it has evolved into a much more pharmacologically based science, impacting on almost every stage of the drug discovery and development process
Pharmacokinetics
The process by which a drug is absorbed, distributed, metabolized, and eliminated by the body.
Pharmacokinetic Principles
● Steady State
● Drugs with short half-life reach steady state rapidly;
drugs with long half-life take days to weeks to reach steady state
Pharmacokinetic types :
Linear Pharmacokinetics
● Linear = rate of elimination is proportional to amount of drug present
Nonlinear Pharmacokinetics
● Nonlinear = rate of elimination is constant regardless of amount of drug present
Why Study Pharmacokinetics
● Monitor medications
●Decrease the risk of adverse effects while maximizing pharmacological response of medication
●Pharmacokinetics describes how the body affects a specific drug after administration.

Pharmacokinetic properties of drugs may be affected by elements such as
● Absorption,Distribution, Metabolism and Excretion. This is commonly referred to as the ADME .However recent understanding about the drug-body interactions brought about the inclusion of new term Liberation. Now Pharmacokinetics can be better described as LADME.It can be divided into two classes.
●Drug input process
L = Liberation is the process of release of drug from a Formulation.
A= Absorption is a process of a substance entering a bodyThrough the skin, intestinal tract, intravenously, mouth, or inhalation Organ systems involved: Circulatory Respiratory Excretory Digestive Distribution Dependent upon tissue permeability, blood flow, perfusion rate of the tissue, drug binding of plasma proteins and tissues.
●Drug Out put process
D = Distribution is the dispersion or dissemination ofsubstances throughout the fluids and tissues of the body
M = Metabolism is the irreversible transformation ofparent compoundsinto daughter metabolitesChemaical conversion of medication inside the body into substances. Almost all drugs are xenobiotics.
E=Excretion is the elimination of the medicine through urine, bile, breath, skin.

PK modeling
Accurate PK modeling is important for precise determination of elimination rate। The most commonly used pharmacokinetic models are:
1-compartment
2-compartment
One compartment All drugs initially distribute into a central compartment before distributing into the peripheral compartment. If a drug rapidly equilibrates with the tissue compartment we can use the much simpler one-compartment model .ExampleThe distribution phase for amino glycosides is only 15-30 minutes, therefore, we can use a one-compartment model with a high degree of accuracy.
Two compartment Drugs which exhibit a slow equilibration with peripheral tissues, are best described with a two compartment model
Example:Vancomycin is the classic example, it's distribution phase is 1 to 2 hours. Therefore, the serum level time curve of vancomycin may be more accurately represented by a 2-compartment model.
The Impact of Pharmacokinetics Analysis has shown that inappropriate pharmacokinetics was a major contributor to attrition of drugs in the 1990's although it had dramatically improved by early 2000