Pharmacokinetics
Pharmacokinetics is a branch of pharmacology which studies what happens when foreign substances enter the human body. It looks at what happens to the substances when they are administered, up until the point at which they are excreted. In humans, the substances that are normally studied are hormones, toxins or other pharmaceutical agents such as paracetamol or aspirin.
The knowledge of Pharmacokinetics is used to come up with an effective plan on how to administer drugs to patients. Some of the main goals of pharmacokinetics are to enhance the efficiency and reduce the toxicity of drugs.
Pharmacokinetics comprises of 5 pathways, these are: Administration, adsorption, distribution, metabolism and elimination.
Administration in pharmacokinetics is studying how the drug is going to be delivered into the body. A few methods include: Oral, Skin, lungs, eyes, and ears. For a drug to reach the target cells, it must be able to move across membranes and enter the blood stream via adsorption. If the drug has poor solubility or has an inability to pass through cell membranes, then this can affect how well the drugs intended effects work. The membranes that separate tissues from blood capillary’s are composed of lipids, this means that lipid soluble drugs will readily cross these membranes, whereas ionised drugs will not. Absorption also links into drug administration, as if a drug that was taken orally did not get adsorbed properly by the body, then it signals the means for the drug to be administered in other desirable ways such as IV or inhalation.
Distribution is studying which tissues/organs the drug gets distributed to when it enters the body. Because the drug has to pass through many different tissues to reach its target site, it tends to lower its plasma concentration. Some factors that can affect the drugs distribution are polarity and molecular size. When the drug enters the body, it is metabolised and goes through chemical alterations. All oral drugs must cross membranes and this is determined by lipid solubility, area available for absorption and specific carriers for Phase 2 metabolism. To calculate distribution you can use the following equation: Volume of distribution = Amount of drug administered / Initial drug concentration.
When substances enter the body, the majority of small molecule drugs get broken down and metabolised by metabolic enzymes such as cytochrome P450 in the liver. When the substance gets broken down, they are converted into smaller, new compounds called daughter metabolites. These new compounds are normally more pharmacologically active than their original parent form. There are 2 phases that drugs go through when they are being metabolised. The first phase involves the oxidation and reduction of the drug to make it more water soluble. After this phase completes however, the metabolites are inactive. Phase 2 then couples the metabolites to other water soluble molecules which makes them pharmacologically active again. There are however, factors that can also compromise an oral drug’s effectiveness and this is called the ‘First Pass’ effect. The First Pass effect happens during drug metabolism whereby the concentration of the drug is drastically reduced before it gets to the target cells. This is mainly due to when the drug passes through the liver, as the liver also plays a role in metabolising drugs. There are methods of delivering drugs that bypass the ‘First Pass’ effect, and these include: Rectal application, volatile anaesthetics, nasal inhalations, injections and IV.
Eventually the drug needs to be removed from the body as a build-up of the foreign substances could affect normal metabolism. There are 3 main ways that drug excretion can occur. The first way is via the urine, this is possible due to ultrafiltration which is carried out by the nephron in the kidney’s. Biliary excretion is another form of drug excretion that initiates in the liver and ends up in the gut where it passes out the body in faeces. The final method of excretion is through the lungs.
Bioavailability is an important area of pharmacokinetics as it looks at the extent and rate that a drug enters systemic circulation to reach the target cell. The bioavailability of a drug depends on various factors, it is mainly affected by the drug form but is also affected by how the drug is manufactured. The equation for drug bioavailability is as follows: F = Amount of drug absorbed by systemic circulation following oral administration / amount of drug absorbed when same dose is administered by IV.
Clearance refers to the elimination of a drug from the body, the equation for this is: Clearance = Rate of elimination / plasma concentration of drug. To calculate the removal of the drug from the blood plasma you need to look at the order that the concentration is decreasing by, e.g zero order or first order. In zero order kinetics, the rate of elimination is constant as the drug has a constant half-life. In first order kinetics however, the elimination of the drug is proportional to the drug concentration and you get an exponential decay.
Overall, pharmacokinetics is very important in looking at what happens to a drug upon entering the body. It gives you an insight on what can make a particular drug effective such as the administration techniques, and also what can handicap it’s effects like its polarity or molecule size. Knowing the pharmacokinetics of drugs is vital as it could be the difference between a drug not being able to help a patient, to harming them.

References
Basic Pharmacokinetics. Available: http://www.ashp.org/DocLibrary/Bookstore/P2418-Chapter2.aspx. Last accessed 07/03/2014.
Expert, T. (2011). What is Pharmacokinetics?. Available: http://hosted.comm100.com/knowledgebase/What-is-Pharmacokinetics-_A99.aspx?id=99&siteid=95439. Last accessed 07/03/2014.
Introduction to Pharmacokinetics and Pharmacodynamics. Available: http://www.ashp.org/DocLibrary/Bookstore/P2418-Chapter1.aspx. Last accessed 07/03/2014.
Le, Jennifer. (2012). Drug Bioavailability . Available: http://www.merckmanuals.com/professional/clinical_pharmacology/pharmacokinetics/drug_bioavailability.html. Last accessed 07/03/2014.