Ladmer System Illustration Essay

Perumal, Omathanu P., Haywood, Alison, Glass, Beverley, and Ho, Paul Chi-Lui (2011) Pharmacokinetics and biopharmaceutics. In: Garg, Sanjay, (ed.) MCQs in Pharmaceutical Science and Technology. Pharmaceutical Press, London, UK, pp. 41-86.

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[Extract] Oral dosage forms are widely used due to the convenience of drug administration. There are several steps a dosage form/delivery system has to undergo before it produces a therapeutic response. This can be explained by the LADMER system which includes liberation of a drug from the dosage form, absorption of the drug, distribution of the drug, metabolism of the drug, excretion of the drug and finally the response. Biopharmaceutics deals with the study of physiochemical and physiological factors that influence the liberation and absorption of drugs from different dosage forms. Pharmacokinetics deals with the absorption, distribution, metabolismn and excretion of a drug; the study of drug response is known as pharmacodynamics. In simple terms, biopharmaceutics is what the pharmceutical scientist does to the drug, pharmacokinetics is what the body does to the drug, and pharmadynamics is what the drug does to the body. Optimisation of biopharmaceutics and pharmacokinetic properties plays a significant role in the development of new drugs. This can be exemplified by the fact that 40% of drug candidates do not make it to market because of poor biopharmaceutical and pharmacokinetic properties. Drug solubility and permeability are the two most important biopharmaceutical properties that influence drug absorption and oral bioavailability. This led to the biopharmaceutics classification system (BCS), which classifies drugs into four classes based on their aqueous solubility and permability. These two properties are determined by sthe drug's physicochemical properties, such as its chemical structure, molecular weight, pKa, partition coefficient, crystal structure and particle size, among others. Drugs with good aqueous solubility and membrane permeability generally show good oral absorption and bioavailability provided the drug is stable in the gastrointestinal tract and does not undergo first-pass metabolism in the liver. Several technologies have emerged to address the poor solubility and permeability of drugs. The important pharmacokinetic parameters that influence the biological performance of dosage forms are volume of distribution, half-life, clearance and fraction absorbed. The volume of distribution and clearance influence the drug's half life, which in turn governs the frequency of drug administration. Clearance and fraction absorbed influence the bioavailability, which in turn determines the dose of a drug. Depending on how the drug is distributed into the body, different mathematical models can be used to characterise the drug disposition and estimate the pharmacokinetic parameters. In oral modified-release systems when or where the drug is released in the gastrointestinal tract is modified. These systems can be broadly divided into delayed-release systems aned extended release systems. In the case of delayed-release systems, the drug release is delayed but not sustained. In the case of extended-release systems, the drug release is sustained or controlled with respect to time, thus reducing the frequency of administration.

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PHA 4121 Biopharmaceutics/Pharmacokinetics

Chapters 1 and 2

Handbook of Basic Pharmacokinetics

·Chapter 1 is a list of terms used in the book.If you want to sound like an expert in pharmacokinetics all you have to do is learn these terms.Remember in science we require very precise definitions.Start learning these terms NOW.

·Chapter 2 -The LADMER system is a way of understanding what goes on in the body when any compound that has an effect on the body is administered or ingested.

See Figure 2-1 on page 12.

The LADMER System is key for us because it is the qualitative way of understanding drug action in a general way.See page 13.

We will come back to the rest of the chapters 3 to 13 after we understant the calculations associated with the models
Most of this is a reflection of the combination of what you already learned in A&P and Pharmaceutics I & II.

Chapter 3
How the body is organized.

To understand how drugs work we first must understand how the body works.Chapter three is a very brief review of the basics of how the body is organized.Remember that form follows function.Therefore the anatomy of the body and its physiology and pathophysiology are linked.You must be able to link these things to be able to understand how the body is reacting to a drug.

Important tissues for this course are the epithelial because they represent the barrier for drug absorption and distribution.We will be dealing mostly with how a drug gets to the biophase and is eliminated not what it does.

Chapter 4 - The Cell Membranes are boundary surfaces that must be crossed by drugs to get to the biophase.

The nature of the cell membrane is discussed on page 28 & 29.

How is the cell membrane like a layer of surfactant??

What are the key factors that affect the permeability of the membrane?

What is the modified fluid mosaic model of the cell membrane?

What is the blood brain barrier?

How do sorption enhances work? (see pages 32 & 33)

Once a drug has managed to get to the Biophase what happens???

Chapter 5 This is the “R” in LADMER.It summarizes the key points covered in the first module in the pharmacotherapy sequence.(Not really but it does match up with what you will learn in much more detail in PHA 421)


Structural Specific Drugs

Enzyme-Linked & Channel-Linked Receptors

Drug Receptor Theories




Chapter 6 discusses absorption of drugs the “A” in LADMER

Fick’s law describes absorption once the drug is in solution

q = -D A/h K (Co - Ci)

What are the anatomical and physiological factors that affect absorption?

Table 6-1 is a summary of the various ways that a drug might be absorbed.

Passive Absorption

Active Transport – Michaelis-Menten Equation

oConvective Absorption

Facilitated Transport

Ion Pair Transport


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