Pharmacokinetics studies the events that happen to a drug from its administration to the time
it is excreted from the body.
It describes what the body does to a drug.
Pharmacokinetics is one of the 2 major branches of pharmacology, the other being pharmacodynamics,
which describes the effects a drug has on the body.
The journey of a drug through the body involves 4 processes: absorption, distribution, metabolism,
and excretion.
- Absorption is when the drug moves from the site of administration to the bloodstream,
- Distribution is how the drug is distributed from the bloodstream to body’s tissues,
- Metabolism describes how the body chemically modifies the drug,
- and excretion is how the drug is eliminated from the body.
Because a drug typically has to be metabolized before it can be excreted, drug metabolism
and excretion are sometimes collectively referred to as clearance.
Pharmacokinetics of a drug depends on its properties as well as patient-related factors.
For example, older patients or those with kidney or liver problems may have slower clearance
rates, causing some drugs to stay longer in their blood.
Knowledge of pharmacokinetics helps determine the optimal drug dosage for individual patients,
as well as the most suitable formulation and/or route of administration for a specific therapeutic
goal.
Drug absorption varies depending on the route of administration, the drug’s chemical properties,
formulation, and patient factors.
When a drug is given intravenously, it absorbs immediately, reaching maximum concentration
in the blood plasma almost instantaneously.
This is not the case with other routes of administration, in which the drug needs some
time to get into the bloodstream, and drug concentration in blood plasma increases gradually.
The maximum, or peak, plasma concentration is reached when drug absorption rate equals
clearance rate.
Peak time, when peak concentration occurs, is an indicator of absorption rate - the faster
the absorption, the sooner the peak time.
Oral administration is the most common route because of its convenience, but it may not
be suitable for some drugs.
Drugs given orally must survive the action of stomach acid and digestive enzymes.
Peptide drugs, such as insulin, are easily degraded in these conditions and cannot be
given orally.
Absorption of oral drugs involves transport across membranes of epithelial cells in the
digestive tract, primarily the small intestine.
Cell membrane is a barrier that all drugs must overcome to get into the bloodstream,
unless they are injected intravenously.
Cell membranes consist mainly of lipids and are therefore hydrophobic.
They are permeable to small non-polar and uncharged polar molecules, but non-permeable
to large polar molecules and charged particles.
Most drugs are weak organic acids or bases.
They alternate between un-ionized and ionized forms depending on the pH of the surrounding
environment.
The un-ionized form is usually lipid-soluble and can diffuse across cell membranes, while
the ionized form cannot.
A weak acid exists predominantly in un-ionized form in the low pH of the stomach so it absorbs
readily through the gastric mucosa.
A weak base, on the other hand, absorbs more easily in the small intestine where the pH
is higher.
Large polar molecules and ionized particles must use special channels or transporters
to move through cell membranes.
There are several ways this can be achieved, but because these transportation facilities
are meant for endogenous substances such as glucose and amino acids; only drugs that resemble
these substances can hijack and use them.
All drugs must be in solution to be absorbed.
Drugs in solid forms must first be dissolved.
The rate of dissolution can be the limiting factor if it is slower than absorption.
For example, sustained-release forms are specifically designed to dissolve slowly, releasing small
amounts of the drug as it passes through the digestive tract.
The goal is to produce a steady level of plasma drug concentration, to have a stable therapeutic
effect with minimum toxicity.
Chewing a sustained-release tablet can release large amounts of the drug at once and may
potentially be dangerous.
A measure of the extent and rate of absorption is bioavailability.
Bioavailability is usually referred to as the fraction of the administered drug that
is absorbed into the bloodstream and is therefore available to the target tissue.
A drug given intravenously immediately enters the systemic circulation and therefore has
a bioavailability of 100%.
An orally-administered drug, on the other hand, must pass through the intestinal wall
and is subject to elimination by the liver before it can reach the systemic circulation,
so its bioavailability is significantly lower.
Bioavailability is usually calculated as the area under the “plasma concentration versus
time” curve, AUC.
Because bioavailability of a drug is considered 100% when delivered intravenously, bioavailability
of a drug given other ways can be calculated by dividing its AUC by the AUC of the same
drug given intravenously.
Bioavailability of a defined drug form also depends on patient factors.
For example, bioavailability of oral drugs is lower in people with digestive problems
or previous gastrointestinal surgeries.
The use of nitroglycerin in angina management is an example of how different routes of administration
result in different bioavailabilities and therefore producing different therapeutic
effects.
Sublingual nitroglycerin diffuses immediately into the bloodstream, producing a fast, strong,
but short-lived action, and is typically used for immediate angina relief.
On the other hand, oral nitroglycerin absorbs slowly, resulting in weaker but more sustained
effects, and is usually prescribed for preventive purposes.