Pharmacokinetics

Habari Future Doctor! Welcome to the World of Pharmacokinetics!

Ever wondered what happens to a Panadol tablet after you swallow it? It doesn't just magically find your headache and zap it away! There's a whole journey it takes through your body. Think of it like a passenger hopping into a matatu at Kencom. Where does it go? Which routes does it take? When does it finally alight? That, my friend, is the essence of Pharmacokinetics.

Simply put, Pharmacokinetics is what the body does to the drug. It's the story of the drug's adventure through you. We break this journey down into four main stages, which you can remember with the acronym ADME.

• A - Absorption
• D - Distribution
• M - Metabolism
• E - Excretion

Let's get on this ride and explore each stage! Fasten your seatbelts!

A for Absorption: Getting on the Matatu

Absorption is the process of the drug moving from the site of administration (e.g., your stomach) into the bloodstream. It's like our passenger (the drug) getting onto the matatu (the bloodstream) to start their journey.

The route of administration matters a lot!

• Oral (by mouth): This is the most common route. But the drug has to survive the "acidic traffic jam" of the stomach and get absorbed in the intestines. Taking a drug with a heavy meal like ugali can sometimes slow down its absorption.
• Intravenous (IV): This is like having a special V.I.P. pass. The drug is injected directly into the bloodstream. Absorption is 100% and immediate! It completely bypasses the gut.
• Topical (on the skin): Like applying a cream. The drug is absorbed slowly through the skin.

Image Suggestion: An infographic-style illustration. On the left, a person is taking a pill with a glass of water, with an arrow pointing to the stomach and then intestines, labeled 'Oral Route (Slow Absorption)'. On the right, a nurse is administering an IV drip to a patient's arm, with an arrow pointing directly into a vein, labeled 'IV Route (Instant Absorption)'. The style should be clean, with vibrant colours common in Kenyan educational materials.

A key concept here is Bioavailability (F). It's the fraction of the administered drug that actually reaches the systemic circulation (the main bloodstream). For IV drugs, F = 100% or 1. For oral drugs, it's usually less than 100% because of incomplete absorption and something called the "first-pass effect," which we'll discuss under Metabolism.

Bioavailability (F) = (AUC oral / AUC IV) x 100%

Where:
AUC = Area Under the Curve (from a plasma concentration-time graph)

D for Distribution: The Matatu's Route Through the Estates

Once in the bloodstream, the drug travels throughout the body. This is distribution. Our matatu is now moving, and the passenger (drug) can visit different "estates" (tissues and organs) like the brain, muscles, and fat.

Some factors affecting distribution include:

• Blood Flow: Organs with high blood flow like the brain, liver, and kidneys get the drug first. It's like the main highways (Ngong Road, Thika Road) getting the most traffic.
• Plasma Protein Binding: Some drugs are like "social butterflies"; they bind to proteins (especially albumin) in the blood. Only the unbound or "free" drug is active and can leave the bloodstream to do its job.
• Lipid Solubility: Fat-soluble (lipophilic) drugs can easily cross cell membranes and enter tissues, including crossing the blood-brain barrier.

Real-World Scenario: Think about the anaesthetic drug, Thiopental. It's very lipid-soluble. When given via IV, it rushes to the brain (high blood flow) and puts a patient to sleep in seconds. But then, it quickly redistributes to fatty tissues, and the patient wakes up. The drug didn't disappear; it just moved to a different neighbourhood!

To quantify this, we use the Volume of Distribution (Vd). It's a theoretical volume, not a real one! It tells us how extensively a drug is distributed in the body's tissues versus the plasma.

Volume of Distribution (Vd) = (Amount of drug in the body) / (Plasma drug concentration)

A high Vd means the drug loves to hang out in the tissues.
A low Vd means the drug prefers to stay in the blood.

M for Metabolism: The Body's "KRA" Office

Metabolism (or biotransformation) is the process of chemically changing the drug into a different compound, usually to make it easier to excrete. The primary site for this is the liver. Think of the liver as the body's strict processing office or factory.

The goal is usually to convert lipid-soluble drugs into more water-soluble (polar) compounds so the kidneys can easily flush them out.

        ASCII Diagram: The Liver's Job

[Lipid-Soluble Drug]  ----(Metabolism in Liver)----> [Water-Soluble Metabolite]
   (Hard to excrete)                                  (Easy for kidneys to excrete)

Remember the First-Pass Effect we mentioned? When you take a drug orally, it's absorbed from the gut and goes straight to the liver via the portal vein before it reaches the rest of the body. The liver metabolizes a portion of the drug before it ever gets a chance to work. This is why the bioavailability of many oral drugs is low.

Image Suggestion: A cartoon diagram of the human torso. Show a pill entering the stomach, then being absorbed into the portal vein which leads directly to a large, prominent liver depicted as a busy factory with workers (enzymes). After the liver-factory, only a small amount of the drug is shown entering the main circulatory system. Label the process 'First-Pass Metabolism'.

E for Excretion: Alighting at the Final Stop

Excretion is the final removal of the drug and its metabolites from the body. Our passenger has finished their business and is now alighting from the matatu.

The main routes of excretion are:

• Kidneys (Renal Excretion): This is the superstar of excretion! The kidneys filter the blood and remove water-soluble substances into the urine.
• Liver (Biliary Excretion): Some drugs are excreted by the liver into bile, which then enters the intestines and is eliminated in the feces.
• Other routes: Lungs (for anaesthetic gases), sweat, and saliva play minor roles.

Now, let's tie this all together with some crucial parameters you'll use every day as a clinician.

Key Pharmacokinetic Parameters & Calculations

Understanding these numbers helps us decide the dose, frequency, and route of administration for a drug. It's the math that saves lives!

1. Clearance (CL)

Clearance is the measure of the body's ability to eliminate a drug. It's the volume of plasma cleared of the drug per unit time (e.g., mL/min or L/hr). It's NOT the amount of drug removed.

Clearance (CL) = Rate of Elimination / Plasma Concentration (C)

2. Half-Life (t½)

This is one of the most important concepts! The half-life is the time it takes for the plasma concentration of a drug to decrease by 50% (or half).

• A drug with a short half-life (e.g., Paracetamol, ~2-3 hours) needs to be given more frequently.
• A drug with a long half-life (e.g., Digoxin, ~36 hours) can be given once a day.

It takes about 4-5 half-lives for a drug to be almost completely eliminated from the body and to reach a steady state with regular dosing.

        ASCII Graph: Drug Half-Life

Concentration |
  100mg       | X
              | .
   50mg       | . . . . X
              |         .
   25mg       |         . . . . . X
              |                   .
  12.5mg      |                   . . . . X
--------------|-----------------------------------> Time
              t=0       t=t½      t=2t½     t=3t½

The formula connecting Vd, CL, and t½ is crucial:

t½ = (0.693 * Vd) / CL

Where:
0.693 is the natural logarithm of 2.
Vd = Volume of Distribution
CL = Clearance

Putting It All Together: The Patient

Why do we learn all this? Because every patient is different! An elderly patient might have reduced kidney function (decreased excretion), meaning a drug stays in their body longer. A patient with liver cirrhosis will have impaired metabolism. Your understanding of pharmacokinetics will help you adjust drug doses to make them safe and effective for each individual.

Think About It: You have two patients with a bacterial infection, both needing Gentamicin. One is a healthy 25-year-old rugby player from Kenya Harlequins. The other is a 75-year-old shosh with known kidney issues. Would you give them the same dose? Absolutely not! The shosh's reduced kidney function means lower clearance, a longer half-life, and a higher risk of toxicity. You would need to give her a smaller dose or increase the interval between doses. This is pharmacokinetics in action!

Congratulations! You've completed the drug's journey from a simple tablet to its final exit. You've seen what the body does to the drug. Keep reviewing ADME, and soon it will become second nature. You are well on your way to becoming a fantastic, thoughtful clinician!