PHARMACOKINETICS-FUNDAMENTALS-PART-1

PRINCIPLES OF PHARMACOKINETICS

Pharmacokinetics is better defined as the action of the body on the drug from its entry point to its exit point.

The actions of the body can be better classified as Absorption, Distribution, Biotransformation(Metabolism)

and Excretion.

Absorption

Absorption can be better explained as the rate at which the drug is moved from its site of administration into the body.

Factors Affecting Absorption

The rate and efficacy of absorption can be affected by the following factors.

1.Route of Administration:-

At the following sequences, the routes affect the absorption

Sublingual<Buccal<Oral<Dermal<Intradermal<Subcutaneous<Intramuscular and other parenteral <Intravenous.

From the above sequences we come to know that the most effective absorption happened at the intravenous route. The drug is 100% absorbed directly into the system by that route.

2.Blood Flow:-

In a highly vascularized area with heavy blood flow such as in small intestine the absorption is more.

3. Surface Area Available:-

The drug absorption is high at higher surface area available.

4.The solubility of a Drug:-

The ratio of the lipophilic to hydrophilic (Partition Coefficient) will decide whether the drug can permeate into a cell membrane. In short a drug that has higher lipophilic moiety will easily pass into the cell membrane to be absorbed.

5.Drug-Drug Interactions:-

When given in combination they may interact which can determine whether to inhibit or enhance the absorption

6.Hydrogen Ion Concentration:

H-ion concentration is usually measured by the negative logarithmic values in the pH scale. The pH of the drug which is acidic or alkaline may affect the absorption.

Many drugs are either weak acids or weak bases and their ionization is partial. Acidic drugs are uncharged when protonated as follows,

                [H+] + [A-] < > [HA] (uncharged)

Basic drugs are charged when protonated as follows

                [B]  + [H+] < > [BH+] (charged)

Generally the uncharged ions are non-polar and lipophilic and can easily pass through the lipid content of the cell membrane. 

Therefore the amount of drugs absorbed depends upon its ratio of charged to uncharged particles which in turn is determined by the ambient pH at the site of absorption and the pKa value which is the negative logarithm of the dissociation constant of the drug.

The fraction of the administered drug available for its biological effect after absorption is known as bioavailability.

The intravenously injected drug has 100% bioavailability as it is completely absorbed into the system.

The first pass hepatic metabolism and all other factors described earlier that affect absorption are also the factors that affect bioavailability.

Routes Of Drug Administration

1.Alimentary canal

2.Parenteral(Injections,infusions etc.etc.)

3.Inhalation

4.Topical (Skin)

5.Transdermal

Types of Alimentary Routes:-

1.Oral

2.Buccal

3.Sublingual

4.Rectal

Types Of Parenteral Routes:-

1.Intravenous

2.Intramuscular

3.Subcutaneous

4.Intradermal

5.Intrathecal

Many pulmonary agents are preferred for administration through inhalation.

Many drugs to be used for local skin applications are preferred by topical routes.

Many sustained-release drugs are used through the trans dermal route.