Pharmacokinetics Decoded: A Med Student’s Guide to Surviving Absorption & Bioavailability

Hey future docs! 👋 Let’s tackle the absorption chapter of pharmacokinetics—the part where I almost drowned in equations but finally saw the light (spoiler: Henderson-Hasselbalch isn’t that evil). Grab your coffee, and let’s simplify this!  

Absorption 101: Why Lipid Solubility is Your New Bestie

Imagine drugs as partygoers trying to sneak into a club (your bloodstream). The bouncer? Cell membranes (mostly lipids).  

- Lipid-soluble drugs (non-ionized): VIP access.  

- Water-soluble drugs (ionized): Stuck in line.  

Pro tip: Acidic drugs (like aspirin) party in the stomach (acidic pH = non-ionized). Basic drugs (like morphine) chill in the intestine (basic pH = non-ionized). 💡  

1. Acidic Medium and Acidic Drugs: Non-ionized → Lipid-soluble → Crosses easily.
2. Acidic Medium and Basic Drugs: Ionized → Water-soluble → Less likely to cross.
3. Basic Medium and Acidic Drugs: Ionized → Water-soluble → Less likely to cross.
4. Basic Medium and Basic Drugs: Non-ionized → Lipid-soluble → Crosses easily.

Translation: Drugs absorb best where their pH matches the environment.When the medium is same ,Then the drug will cross.

The medium in which the drug is present (acidic or basic) affects its solubility and, therefore, its absorption.Lets take water, as an example.Water can resesides in two forms inside any medium, it can be H2O (non ionized/non polar form) or H+ and OH- ions(ionized and polar form).Likewise any drug can also resides in two forms, non ionized/non polar or ionized/polar forms,HX or H+ and OH-.And it depends on medium where the drug is, acidic or basic medium.

Thus,if the drug is Ionized, it is water soluble and if the drug is non ionized , it is lipid soluble. And we have studied that lipid soluble drug can paas through the membranes.

Henderson-Hasselbalch Equation: The pH vs. Drug War

This equation predicts how much drug gets absorbed based on pH. Here’s the cheat code.

This equation predicts the ratio of ionized to non-ionized forms of a drug in different pH environments.It tells how drugs act in different media.

Acidity depends on pH.So,according to pH solubility will also be different.If we want to know exactly, how much , then we must know Nature of drug,pH, and Pka of drug.

With this formula,

We can draw this table,and see how drug is soluble in different pH.

Basically,this formula tells,how drugs act in different media.And with this table,you can see,drug can not be fully soluble in any media and it is different in different pH.Like in pH-6 , 50% drug is lipid soluble, so 50% drug is susceptable to paas through the membranes

However,practically  most drugs are absorbed more efficiently in the intestine than in the stomach due to:

• Large surface area of the intestine.
• Longer retention time of the drug in the intestine.For instance,drug stays around 30 min in stomach where as 6-7 hrs in intestine

Bioavailability: Why IV Drugs Flex on Orals  

Bioavailability- Biologically Available

Bioavailability = % of drug that survives the body’s gauntlet to reach blood.  

Bioavailability refers to the fraction of a drug dose that reaches systemic circulation in its unchanged form. This factor is critical in determining the appropriate dosage of a drug.

High bioavailability of drug means→ Lower dose required.

Low bioavailability of drug means → Higher dose required.

For example,if we give 100 molecules of any drug orally,only 50 molecule reaches to the systemic circulation,then bioavailability is 50 percent.

Absorption: 

Greater absorption leads to higher bioavailability.

Route of Administration:

Oral (5–100% bioavailability)(thanks, first-pass metabolism😒).  

Intramuscular (75–100%).

Subcutaneous (75–100%).

Intravenous (100%)(no obstacles).

First-pass Metabolism: Nitroglycerin gets wrecked by the liver if swallowed. Solution?

 First you have to understand the mechanism.

Mechanism of first-pass metabolism:  

- Occurs when a drug is metabolized by the liver/GI tract before entering systemic circulation.  

- After oral ingestion, drugs are absorbed via the gut → transported to the liver via the portal vein → metabolized by hepatic enzymes (e.g., CYP450).  

- Result: Reduced bioavailability → lower therapeutic effect unless dose is adjusted.  

Clinical Impact:  

- Drugs with high first-pass metabolism often require higher oral doses or alternative routes (e.g., IV, sublingual, transdermal) to bypass the liver.  

Examples of High First-Pass Drugs

1. Nitroglycerin (GTN): Sublingual for acute angina.  

2. Propranolol (oral, but high first-pass → higher oral doses needed).  

3. Lignocaine (Lidocaine): Given IV/topically (not oral due to extensive first-pass).  

Mnemonic for this Drugs: 

"LPG"

- L: Lignocaine (rarely sublingual; mostly IV/local)  

- P: Propranolol (not standard sublingual; oral/IV)  

- G: GTN (Nitroglycerin) classic sublingual example  

"Note: Mnemonic may emphasize high first-pass drugs, but routes vary!"

Why Sublingual Route Rocks for NTG

1. Rapid absorption→ quick relief in angina emergencies.  

2. Bypasses first-pass metabolism → higher bioavailability.  

3. Self-administered→ patient autonomy.  

4. Excess drug can be spit out→ avoids overdose.  

Clinical Pearls

- NTG is the go-to for acute angina (vasodilates coronary arteries).  

- Propranolol (oral β-blocker) requires dose adjustment due to first-pass.  

- Lignocaine avoids oral route; used IV for arrhythmias or topically.  

Why First-Pass Metabolism Haunts My Nights?

Oral drugs face the liver’s “Hunger Games” before hitting circulation. Result? Some meds need mega doses (or skip the gut entirely). Rectal route? Partial escape… but let’s just say it’s awkward for emergencies.  

How to Calculate Bioavailability?

The bioavailability of a drug administered orally can be calculated by comparing it to the same dose given intravenously (IV).

1. Administer Drug A (e.g., 100 mg) via IV route.
2. Plot a plasma concentration vs. time graph to calculate the area under the curve (AUC).
   
   
   
3. Administer the same dose (100 mg) orally and plot the graph.
   
   
   
4. Bioavailability = Area under the curve in case of oral route/Area under the curve in case of IV route.

Bioequivalence: When Generics Are Almost Twins

When two brands of the same drug have similar bioavailability (difference within 20%), they are termed bioequivalent. This ensures that different brands provide the same therapeutic effect.

 However, exceptions like phenytoin,which is used in the case of epilepsy exist, where bioavailability differences of different brand may impact treatment outcomes.

Plasma Concentration-Time Curve: The Rollercoaster Ride

- Cmax: Peak drug level (don’t cross toxic concentration!).  Maximum concentration achieved by a dose.

• Should fall between minimum toxic concentration (MTC) and minimum effective concentration (MEC).

- Tmax: Time to peak (faster = quicker relief). Time taken to reach Cmax, indicating the rate of absorption.Less Tmax means rate will be faster.

- AUC: Total drug exposure (higher = better absorption). Total area under the graph, representing the extent of absorption.

Plot twist: IV drugs spike instantly; orals take the scenic route.  

Final Med School Hacks

1. Mnemonic: “LPG” for first-pass victims.  

2. AUC Formula: Bioavailability = Oral AUC / IV AUC.  

3. Clinical Pearl: Morphine’s low oral bioavailability = why we IV it post-surgery.  

Pharmacokinetics is like learning a new language—but once you get it, dosing makes sense. You’ve got this! 💪  

Drop your pharma struggles below!

 Let’s rant about HH equations together. 😅  

Thank you.