3.2. Analyse how drug development is informed by pharmacodynamics and pharmacokinetics

This guide will help you answer 3.2. Analyse how drug development is informed by pharmacodynamics and pharmacokinetics.

Drug development is the process of researching, creating, and introducing new medicines. It involves several complex steps to ensure drugs are effective, safe, and suitable for use in humans. Two core branches of science that guide drug development are pharmacodynamics and pharmacokinetics. These disciplines help researchers design drugs that work correctly while reducing side effects and dosing complications.

Understanding what these terms mean and their roles in drug development is important for recognising how advancements in healthcare are made possible.

What is Pharmacodynamics?

Pharmacodynamics (PD) is the study of how drugs affect the body. It focuses on the biochemical and physiological reactions of the body when exposed to a drug. These reactions determine the drug’s therapeutic effects, such as relieving symptoms or curing a condition.

Key factors studied in pharmacodynamics include:

• The drug’s mechanism of action: This explains how the drug interacts with cells and tissues. For example, many drugs work by binding to receptors on cells to trigger specific responses.
• Desired effects: These are the positive, intended effects of the drug, like pain relief or reduced inflammation.
• Side effects: These refer to any unintended effects, such as nausea or drowsiness. Understanding these is critical in developing safe drugs.
• Dose-response relationship: This watches how different doses of a drug impact its effects. It determines the minimum dose needed for the drug to work and the highest dose before it causes harmful effects.

Pharmacodynamics, in simple terms, shows what a drug does to the body. This knowledge allows scientists to select or modify compounds that will bring the greatest benefit with the least harm.

What is Pharmacokinetics?

Pharmacokinetics (PK) is the study of how the body affects a drug after it has been administered. It explains how a drug is absorbed, distributed, metabolised, and excreted from the body. This process is often remembered as ADME, which stands for:

1. Absorption: How the drug enters the bloodstream. For example, does the drug need to be taken as a pill, injected into the bloodstream, or absorbed under the tongue?
2. Distribution: How the drug moves through the body and reaches the site where it is needed.
3. Metabolism: How the drug is broken down or transformed by the liver or other organs.
4. Excretion: How the body eliminates the drug, usually through urine, faeces, sweat, or breath.

Pharmacokinetics provides valuable information about how long a drug stays in the body, how quickly it starts working, and how often a person will need to take it.

Working together with pharmacodynamics, pharmacokinetics helps researchers balance the effectiveness of a drug with its safety.

The Role of Pharmacodynamics in Drug Development

Pharmacodynamics is used early in drug development to find compounds that have the desired therapeutic effect. Scientists study how compounds interact with biological targets, such as proteins, receptors, or enzymes. For example, they may explore whether a potential new drug can block a specific protein linked to disease.

Drug developers test the strength of these interactions and identify the most promising compounds. Understanding pharmacodynamics ensures the drug interacts with targets in a way that meets the desired outcomes.

For example:

• Cancer drugs (chemotherapy) may work by preventing cancer cells from dividing. The pharmacodynamics of these drugs are centred on destroying abnormal cells while leaving healthy cells unharmed.
• Anti-inflammatory drugs like ibuprofen work by inhibiting inflammatory pathways. Researchers use pharmacodynamics to make these medicines more effective and reduce irritation or damage to the stomach lining—a common side effect.

Pharmacodynamics also helps determine if a drug produces the effects uniformly across populations or only works on specific groups, such as those with particular genetic traits.

The Role of Pharmacokinetics in Drug Development

Pharmacokinetics is critical for determining how a drug should be delivered and at what dose. It ensures the drug reaches the right area in the body and remains there for the correct amount of time to produce its benefits.

Here’s how PK informs drug development at different stages:

1. Absorption studies: These evaluate how well the drug enters the bloodstream after being administered. For example, scientists check if the drug works better as a pill, injection, or topical cream. Poor absorption may mean the drug will not be effective or needs reformulation.
2. Distribution studies: These help determine how much of the drug reaches the target organ or tissue. Some drugs may spread too widely in the body, reducing their effectiveness at the intended site. This process can also highlight if the drug accumulates in an unintended area, increasing risks of toxicity.
3. Metabolism studies: These explore how quickly the drug is broken down. If it metabolises too fast, it might not work long enough to be helpful. If it breaks down too slowly, there’s a risk of it accumulating to dangerous levels. The liver is particularly important since it processes most drugs. Variations in liver enzymes between individuals can impact how medicines are metabolised.
4. Excretion studies: These evaluate how the body removes the drug. Knowing whether a drug is primarily excreted through urine or faeces helps identify risks for people with kidney or liver problems who might not clear the drug efficiently. This can determine if adjustments are required for these individuals.

Pharmacokinetics also helps design drugs that can avoid interactions with other medicines someone may be taking, such as preventing a medicine from being processed too slowly when taken with something else.

How Pharmacodynamics and Pharmacokinetics Work Together

Both pharmacodynamics and pharmacokinetics are essential in making sure drugs work effectively and safely. Scientists must balance these aspects to achieve optimal outcomes. Here’s how they overlap in drug development:

1. Dose optimisation: Pharmacodynamics sets the dose needed to achieve the desired effect, while pharmacokinetics ensures the drug is absorbed, distributed, and maintained in the body at that dose.
2. Timing of dosing: PD and PK help determine how often a person should take the drug. For example, should it be once a day or every few hours? Pharmacokinetics measures how long the drug stays in the body, while pharmacodynamics shows if the drug still works when levels become lower.
3. Managing side effects: Both PD and PK allow researchers to reduce unwanted effects. A drug’s pharmacodynamics might cause side effects if the dose is too high. Pharmacokinetics can be adjusted to carefully control how the drug is released or eliminated.

Case Study: Paracetamol

Paracetamol is an everyday example of how both pharmacodynamics and pharmacokinetics inform drug development.

• Pharmacodynamics: Paracetamol works by inhibiting enzymes in the brain responsible for pain and fever regulation. Researchers ensure it works efficiently without interfering with other enzymes that may cause side effects.
• Pharmacokinetics: It is absorbed quickly from the digestive system and starts working within 30 minutes. It is metabolised in the liver and mostly excreted through urine. Understanding this ensures paracetamol can be effective at standard dosing intervals of four to six hours while avoiding overdose which could harm the liver.

Challenges in Applying PD and PK

While PD and PK are valuable, there are challenges when it comes to applying them in drug development:

• Individual differences: People’s genetics can cause variations. For instance, some may metabolise drugs faster or slower than average, leading to different outcomes.
• Drug interactions: People taking multiple medicines may find that one drug affects the PK or PD of another.
• Special populations: Differences across age groups (children, elderly) or those with medical conditions can make it harder to design universal dosing strategies.

Ongoing research helps address these problems by developing methods to predict how drugs work in diverse populations.

Conclusion

Pharmacodynamics and pharmacokinetics are at the heart of drug development. They allow scientists to create medications that strike an effective balance between treating symptoms and avoiding harmful side effects. By studying how drugs interact with the body and how the body processes them, researchers produce medicines that are safer, more targeted, and easier to use.

Safe and effective drug development relies on mastering the interplay between these sciences. Together, they help bring new medicines to market that improve the quality of life for millions of people.