# Pharmacokinetics

**Pharmacokinetics** is the study of drug movement in the body (the dose-concentration part, whereas pharmacodynamics deals with the concentration-effect part), and involves the studies of *aborption*, *distribution* and *excretion*.
Knowledge of pharmacokinetics (*aka* drug kinetics) is a prerequisite for rational use of any drug used in therapy, and a must for effective therapeutic monitoring of drugs with narrow therapeutic ranges.
It is also useful in the prediction of drug-drug and disease-drug interactions.

## Absorption

For a drug to be effective, it must first be introduced into the body, which can happen via intravenous injection, the oral route, inhalation, subcutaneously, intramuscularly, rectally and transdermally.
The proportion of drug that reaches the systemic circulation in an unaltered form is the bioavailability of the drug (*F*).

Usually, drug absorption is a first-order (linear) process, with the rate represented by the constant K_{a} (total drug aborbed per unit time from the site of administration).
It can be affected by the rate of diffusion from the gastrointestinal tract, which is in turn affected by the partition coefficient (solubility), surface area, and difference in concentration.
Absorption can also be altered by food.
For example, tetracycline taken while fasting is much more effective than when it is taken with milk.
Also, grapefruit juice can affect the rate of absorption of drugs [1], such as its effect in increasing the efficacy of felodipine.

## Distribution

**Distribution** of a drug is measured by the apparent volume of distribution <math>\left ( V_d = \frac{dose}{C_{plasma}} \right )</math>.
This measure is the volume into which the drug *appears* to distribute, though it is obviously not a real volume when compared to the physiological volume capacities involved.
Variation in *V _{d}* is due to the degree of heterogeneity with which the drug is stored or processed across various tissues of the body.
The volume of distribution is necessary for calculating loading doses and for estimating the dose needed to achieve a therapeutic level.

## Elimination

Major contributors to the elimination of drugs include the liver (hepatic metabolism), gut metabolism and transporters.

The *half-life* of a drug is the amount of time required to eliminate half of the drug.
Usually, drugs display first-order elimination properties, meaning that their half-life can be plotted on an exponential curve that can then be straightened by logarithmic manipulation.

**Clearance** <math>\left ( {CL} = \frac{volume}{time} \right )</math> is the volume of circulating blood from which all drug is removed in a unit time.
The rate of clearance affects the half-life, and is usually the largest factor in any change in half-life.

## Drug Accumulation

When drugs are repeatedly administered, drug accumulation must be taken into effect.
This is because it takes an infinite time (in theory) to eliminate all of a given dose.
In practical terms, if the dosing interval is shorter than four half-lives, accumulation will be detectable, since it takes 4-5 half-lives for the drug concentration reaches the plateau, also known as the *steady-state*.
Steady-state is the concentration achieved when the rate of drug input into the body is equal to the rate of output.

Usually, a loading dose is first administered to get the body into the therapeutic range, followed by a maintenance dose.

## Models

There are two relevant pharmacokinetic models: *Single* and *two* compartments.

## Resources

Basic and Clinical Pharmacology (9th Edition; Katzung): 1.4. Drug Biotransformation