THE LADMER SYSTEM

Discuss the overview of the passage of drugs from the liberation of drugs from the dosage form to its
elimination from the body. It discusses what happens to the drug after liberation from dosage forms
taken internally from different routes into the body, the absorption of the drug, distribution, metabolism,
and subsequently the elimination of drug via different routes.

WHAT IS THE LADMER SYSTEM?

The LADMER system stands for Liberation, Absorption, Distribution, Metabolism, Elimination and
Response.

The LADMER system is a complex interrelationship between drug, drug product and the body. Download
the LADMER system and follow the explanation using the diagram.

There is always a relationship between dose and effectiveness or dose response and the pharmacologic
effect of the drug on the amount of drug administered. Before any effect is seen there are many other
factors which are responsible for the entrance of a drug into the body. These factors are based on the
physical and chemical properties of the drug substance and of the drug product.

What happens to the active ingredient in the body after administration of a drug product from various
dosage forms?

The entire cycle of the process is termed as Fate of the Drug.

Whether the drug plasma level curve will peak rapidly or slowly depends on: the route of administration,
the dosage form, the liberation rate of the drug from the dosage form, diffusion, penetration and
permeation of the drug; its distribution within the body fluids and tissues; the type, amount, and rate of
biotransformation, recycling processes and elimination. Other factors are also involved depending on the
individual disposition, diseases and so on.

The fate of the drug is described by the LADMER

Liberation
This is the first step in determining onset of action, rate of absorption, availability and so on. This is true
for all routes of administration, except IV and per oral use of true solutions.
Liberation is controlled by the characteristics of the drug product. As you can see in the diagram the five
processes are underlined.

A drug is administered in a dosage form by any route of administration. This must be released from the
dosage form (except in IV and true solutions) after which the released drug undergo Dissolution.
Dissolution becomes the first and sometimes the rate limiting step.

Upon administration of suspensions, capsules, tablets, suppositories, implants and IM suspension, drug
particles will be found in the gastrointestinal tract (GIT), in the body cavities or in tissues. After
dissolution, the drug diffuses to the site of absorption (e.g., buccal, gastrointestinal, subcutaneous,
intramuscular, intraperitoneal, intracutaneous, ocular, nasal, pulmonal and rectal.
Absorption
Some of the drugs will already be inactivated before it can be absorbed. Only drugs administered IV in
solution enter the circulatory system immediately. With all other routes of administration, the drugs must
pass membranes that act as lipid barriers.

Different transport mechanisms are employed to penetrate into and to permeate through these
membranes. Most of the drugs are absorbed or transported by passive diffusion, which depends on the
pKa value of the drug, the pH of the solution, and the lipid solubility of the unionized form. Drugs passing
through the lipid barrier may enter the central compartment, example after IM, sub-C, IP, IC, nasal, ocular
and pulmonal.

Distribution and Metabolism

Drugs administered perorally and some drugs administered rectally are confronted with enzymes as they
pass through the liver with the blood flow. The liver is the main organ of metabolism. In the liver, some
drugs are inactivated and metabolized during the first pass, others are activated.

Most drugs are at least partially bound to protein in the blood stream. Only the free, unbound drug form of
the drug is available for action. The protein bound is not permanently trapped but is in equilibrium and will
be released from the protein as the free drug is eliminated from the plasma.

The drug may enter the peripheral compartment by again passing a lipid barrier until it reaches the
biophase (process of distribution). The biophase or the site of action is a cell or a cell component, where
the final interaction between drug and receptor takes place.

Elimination
After release of the drug from its receptor binding, the drug again passes through a lipid barrier, enters
the central compartment, from which the drug again passing a lipid barrier, is metabolized in the liver or
kidney or in the tissue or plasma..

It then either passes via biliary excretion into the intestines or passes through the kidney, where it will
either be reabsorbed or finally excreted in the urine.

Elimination is not only by urinary means but also through the salivary glands, the milk glands, the sweat
glands and the lungs.

Reabsorption takes place not only by urinary and biliary means but also in the intestine after
enterohepatic cycling, if the drug or its metabolites is in absorbable form.

Response
All these factors are involved whether the drug administered will produce a therapeutic effect, yield only a
subtherapeutic effect or even slow toxic effect.

THE LADMER SYSTEM IS THE KEY FOR THE FOLLOWING TASKS

Knowledge and understanding of the LADMER system enables the pharmaceutical scientist to:
1. Develop new active compounds, analogs or derivative
2. Develop dosage forms with desired release characteristics.
3. Determine the pharmacokinetic parameters and pharmacokinetic drug profiles,
4. Determine and evaluate the bioavailability
5. Select the most appropriate route of administration
6. Determine the effective dose sizes
7. Adjust the dosage regimen to achieve a desired therapeutic concentration. (e.g., body weight,
age, sex) and pathologic (e.g., renal, hepatic or heart failure, obesity, malnutrition) factors.