What is Pharmacokinetics?

Pharmacokinetics is made up of two words: pharmakon means drug, and kinetics which means moving. Pharmacokinetics could be defined in simple words as the movement of drugs through the whole body and out of the body.

Process Involved in ADME (Absorption, Distribution, Metabolism, and Excretion)

The pharmacokinetics processes include four main sub-processes, which include absorption of drugs followed by their distribution, metabolism of drugs, and lastly, the elimination of drugs from the body. All sub-process involves the movement of drugs across the plasma membrane. So, it can be concluded that plasma membranes play an important role in pharmacokinetics.

I. Absorption

Absorption is the first step in the pharmacokinetics of drugs inside the body, where the movement of drugs takes place from the site of the drug adsorption to the blood. Most drugs are administered orally, and other drugs are taken through different routes like intravenous, sublingual, buccal routes, etc. Most drugs are absorbed in the target cells by passive transport as they are lipid-soluble, but few drugs are absorbed by active transport as they are non-lipid in their chemical nature.

The cell plasma membrane is composed of phospholipids, allowing easy absorption of lipid-soluble drugs across the cell. Therefore, we can conclude that lipid-soluble drugs are absorbed more efficiently as compared to non-lipid drugs. Drug absorption is used to determine the bioavailability of drugs. Bioavailability is the degree and rate at which a drug is absorbed and reaches the systemic circulation. Systemic circulation involves the flow of oxygenated blood from the heart to different parts of the body and the flow of impure blood from other parts of the body to the heart. Systemic circulation allows easy movement of the drug to different parts of the body from the administration site.

Another parameter that decides the absorption of the drug is the pH of the drug. The acidic drug is better absorbed in the stomach, and basic drugs are absorbed in the small intestine. For example, aspirin is absorbed in the stomach, and morphine is absorbed in the small intestine. One protein that is highly important in drug absorption is P-gp (p-glycoprotein). P-gp is an ABC-type efflux protein present in the plasma membrane of human cells, which determines the amount of drug absorbed and excreted from the target cells.

II. Distribution

Once the drug is absorbed inside the blood, it reaches the target tissue by systemic circulation with blood movement as it delivers oxygenated blood to different parts of the body. As the distribution progresses, the drug plasma concentration decreases. The distribution of drug depends on different factors such as whether the drug can cross the blood-brain barrier, the difference in blood flow rates across the different parts of the body, the molecular size of the drug (the small size molecule is distributed fast as compare to the big molecule), the polarity of the drugs (more polar is less distributed as compare to less polar). For example, aminoglycosides are polar drugs that cannot cross the plasma membrane effectively.

III. Metabolism

The metabolism of the drug is also known as biotransformation. It is the process where the drug is transformed in the body to make it more hydrophilic or water-loving to be excreted outside the body. The kidney is the excretory organ involved in its excretion. The excretion of a drug from the body is required because it is a chemical substance that is not a part of the body and has to be excreted as soon as its function is over. The drug metabolism mainly takes place in the liver and the kidney. Therefore, if any person has any problems in the liver and kidney, they have high levels of the drug in their body and need to be monitored. Metabolism involves specific enzymes that modify the drug so that it can excrete efficiently from the body. Based on the type of chemical modification performed by the enzymes, the drug metabolism could be divided into two phases: phase I metabolism and phase II metabolism.

Phase I: Metabolism

In this type of metabolism, the drug is chemically modified by the processes like reduction, oxidation and hydrolysis, and functional group removal.

Phase II: Metabolism

In this type of metabolism, enzymes catalyze the addition of polar groups to the drugs to be readily soluble in water and get easily removed from the body.

IV. Excretion

The last step in drug pharmacokinetics is its excretion or removal from the body. The drug is mainly excreted from the kidney or by the renal pathway, but some drugs are excreted as sweat, saliva breathes, etc. If a drug is not excreted from the body, it could cause toxicity in the body.

Toxicity

We also have to study the toxicity of the drug in pharmacokinetics. This is because it is used to find the relationship between the degree and risk of drug toxicity.

Pharmacokinetics Parameter

There are four main parameters involved in evaluating the processes involved in the pharmacokinetics of a drug, and these parameters are referred to as PK Parameter (Pharmacokinetics Parameters). These parameters include the bioavailability of the drug, the volume of distribution of the drug, the half-life of the drug, and drug clearance. As the liver and kidneys are involved in drug metabolism, PK parameters are calculated for these organs.

I. Bioavailability: is defined as the fraction of the active ingredient of the administered drug, available to the site of action. The study of bioavailability is important to find the putative amount of drug dose. One of the important factors in determining bioavailability is the route of administration. The drug administered intravenously has 100% bioavailability, whereas other routes of administration have less than 100% bioavailability.

II. Volume of distribution (V_d): is used to find the relationship between the amount of drug in the body to the drug concentration in plasma or blood. The volume of distribution is also known as the apparent volume of distribution. This parameter is used to find the amount of drug that will reach the target tissue site and not remain in the plasma. This parameter value is high in lipid-soluble drugs as they can easily enter the target cells compared to non-lipid drugs. The volume of distribution is important in finding the loading dose of a given drug.

III. Clearance of the drug: This is used to find the volume of blood or plasma that is completely clear of the drug per unit time. The unit of drug clearance in mL/min (milliliter per minute) or L/hour (liter per hour). This parameter is required for the drug excretion by renal mode along with other metabolic pathways. The renal mode is the most common route for drug clearance.

IV. Half-life of the drug: is defined as the time period required by the drug to get reduced to half (50%) of the initial amount of drug concentration administered in the plasma. T1/2 represents the half-life of a drug. The half-life of the drug is important to formulate the drug dosage and dosing interval of the drug.

During clinical trials, the patient's plasma drug concentration vs. time profile can be drawn by measuring the plasma concentration at several time points.

Pharmacology

This is the branch of science where we study the interaction of any chemical molecule that enters inside the body of an organism with the biological system. This branch is further divided into two parts: pharmacodynamics and pharmacokinetics.

Pharmacodynamics involves the study of the effects of the drugs on the body, and pharmacokinetics involves how the body where the drug was administered affects the drug. Both are used in the formulation of drugs by scientists, so it is very much required to study both branches of pharmacology. The pharmacodynamics is also important to find the systematic exposure of the drug that is further used to study drug-drug interaction. The most common pathway of interaction between drugs is with tissue receptors that are present in the cell membrane. The pharmacodynamic studies help characterize the pharmacological effects of a drug, establish the duration of response, and dose-response to the effect.

Application of Pharmacokinetics for Oral COVID-19 drug  

Pfizer pharmaceutical company has recently announced that they have begun the early-stage trial for oral COVID-19 drug. This drug belongs to the class of drugs known as protease inhibitors. The pharmacokinetics methods: absorption, distribution, metabolism, and elimination of this drug are under study to find the efficacy of this drug and an oral dose of the drug. Also, the pharmacodynamics of drugs is crucial to study the drug efficacy.

One of the main constraints in drug metabolism is the first-pass metabolism that takes place in the liver. It leads to a decrease in the concentration of the drug before it reaches the systemic circulation. In these cases, the constant drug dose sometimes increases the efficacy of a drug, and this phenomenon is known as drug exposure.

Context and Application

1. For Bachelor of Science in Biology: The pharmacokinetics is very important for studying the drug and its activity inside the body of humans and other animals. Renal excretion is important to study drug clearance.

2. For Master of Science in Microbiology: As most of the diseases are infectious in nature (means caused by microbes), so drugs are designed to inhibit the action of unique microbial protein and to study pharmacokinetics is very important for these students. The student will also study pharmacodynamics that is used to find the drug's systematic exposure.

3. For Master of Science in Microbial Biotechnology: The students of microbial biotechnology will learn to use the techniques in designing the drug and studying the pharmacokinetics parameters, plasma drug concentration.