Introduction:
This is Part 2 of Pharmacokinetics Notes: Excretion and Elimination of Drugs, Bioavailability | MSc Chemistry 4th Semester.
This topic is a part of the Medicinal Chemistry paper of the MSc Chemistry syllabus (BAMU University and other universities). In this section, you will learn about the major routes of drug excretion, factors affecting bioavailability, and their clinical importance. These notes are written in simple language to help students understand the concepts clearly and prepare well for university exams and competitive exams.
📚Topic cover in this post:
1)Introduction
2)Elimination of Drug
3)Excretion of Drug
4)Bioavailability
5)Summary
6)FAQS
Elimination of Drugs
Definition:
Elimination is the process by which a drug is removed from the body.
👉 It includes two main steps:
1. Metabolism (Biotransformation) – Chemical change of the drug (mainly in the liver).
2. Excretion – Physical removal of the drug or its metabolites from the body.
#Excretion of Drugs
Drug excretion is the process of eliminating a drug or its
metabolites from the body. The major routes of excretion
include the kidneys (urine), liver (bile/feces), lungs (exhalation),
and minor routes like sweat, saliva, and breast milk.
A) Renal (Kidney) Excretion (Major Route)
The kidneys play a major role in drug excretion through urine.
This process occurs in three steps
1. Glomerular Filtration:
• Drugs that are free (unbound) in the plasma are filtered
by the glomerulus into the renal tubules.
• Protein-bound drugs do not get filtered.
2. Tubular Reabsorption:
• Lipid-soluble drugs are reabsorbed into the blood by
passive diffusion.
• Water-soluble and ionized drugs remain in the urine and
are excreted.
3. Tubular Secretion:
• Some drugs are actively secreted into the renal tubules
using transporters (e.g., penicillin, uric acid).
• This increases the elimination of certain drugs.
Effect of Urine pH on Excretion:
1. Acidic urine increases the excretion of basic drugs (e.g.,
amphetamines).
2. Alkaline urine increases the excretion of acidic drugs (e.g.,
aspirin).
3. Urinary pH can be altered to enhance drug elimination in
cases of ovoverdose.
B)Hepatic (Liver) Excretion
• The liver metabolizes drugs and excretes them into bile.
These drugs enter the intestines and may be reabsorbed
(enterohepatic circulation) or eliminated in feces.
• Drugs with large molecular weight, like steroids and bile
salts, follow this route.
C)Pulmonary (Lung) Excretion:
• Volatile drugs and gases (e.g., anesthetic gases, alcohol)
are excreted through exhalation.
• The rate of excretion depends on the solubility of the
drug in blood and the rate of respiration.
D) Other Minor Routes
• Sweat and Saliva: Some drugs (e.g., heavy metals,
nicotine) are excreted through sweat or saliva.
• Breast Milk: Drugs can pass into breast milk, which can
affect infants. Lipid-soluble and basic drugs (e.g.,
tetracyclines) are more likely to be excreted in milk.
Clinical Importance of Drug Excretion:
1. Impaired kidney function slows down drug excretion, increasing the risk of drug accumulation and toxicity.
2. Urine pH manipulation is used in cases of poisoning to enhance drug elimination.
3. Drugs excreted in bile may undergo enterohepatic
circulation, prolonging their effect
Bioavailability
Definition:
Bioavailability (F) is the fraction or percentage of an
administered drug dose that reaches systemic circulation in
an active form. It is an important pharmacokinetic parameter
that determines the effectiveness of a drug.
Types of Bioavailability:
1. Absolute Bioavailability (F)
Compares the bioavailability of a drug given via a non-IV
route (oral, intramuscular, etc.) with its bioavailability when
given intravenously (IV).
Formula:
F=AUC oral/AUC IV ×100
Example: If an orally administered drug has an AUC of 50 and
an IV form has an AUC of 100, its bioavailability is 50%.
2. Relative Bioavailability
1. Compares the bioavailability of one non-IV formulation
with another.
2. Used to compare different dosage forms (e.g., capsule
vs. tablet).
Factors Affecting Bioavailability:
A)Route of Administration:
1. IV (Intravenous): 100% bioavailability (direct entry into the
bloodstream).
2. Oral (PO): Lower bioavailability due to barriers like
digestion, metabolism, and absorption.
3. Sublingual, Rectal, Inhalation: Higher bioavailability than
oral, as they bypass first-pass metabolism.
4. Intramuscular (IM) & Subcutaneous (SC): Moderate
bioavailability, depending on tissue blood flow.
B)First-Pass Metabolism:
1. Drugs taken orally pass through the liver before
reaching systemic circulation.
2. Liver enzymes may metabolize the drug, reducing its
bioavailability.
3. Example: Nitroglycerin has very low oral bioavailability
(~10%) and is given sublingually to bypass the liver.
C)Physicochemical Properties of the Drug:
1. Solubility: Lipid-soluble drugs pass through cell
membranes easily, increasing absorption.
2. Molecular Size: Large molecules may have difficulty
crossing membranes.
3. Stability: Some drugs degrade in acidic stomach conditions
(e.g., penicillin G).
D)Dosage Form & Excipients:
Tablets, capsules, suspensions, and solutions differ in their
dissolution rates.
2. Coatings and excipients can control drug release, affecting
bioavailability.
E) Gastrointestinal (GI) Factors:
pH variations: Drugs that are weak acids absorb better in the
stomach, while weak bases absorb better in the intestines.
Food effects: Some drugs require an empty stomach
(tetracyclines), while others need food (griseofulvin).
f). Blood Flow to Absorption Site:
1. High blood flow improves drug absorption (e.g., muscle
injections absorb faster than subcutandecrease
G). Drug-Drug or Drug-Food Interactions:
1. Some drugs reduce absorption of others (e.g., antacids
can decrease antibiotic absorption).
2. Grapefruit juice inhibits drug metabolism, increasing
bioavailability of some drugs.
Bioavailability Enhancement Strategies:
• Prodrugs: Convert inactive drugs into active forms in the
body to improve bioavailability (e.g., enalapril →
enalaprilat).
• Lipid-based formulations: Increase absorption of poorly
soluble drugs.
• Nanotechnology: Improves drug solubility and
bioavailability.
Importance of Bioavailability in Medicine:
Ensures proper dosing to achieve therapeutic effects.
Helps in drug formulation development (e.g., extended-
release vs. immediate-release).
Reduces side effects by optimizing drug concentration in the
blood.
Examples of Bioavailability in Drugs:
Drug:Morphine
Route:iv
Bioavailability:100%
Drug:Paracetamol
Route:oral
Bioavailability:80%
Drug:Nitroglycerin
Route:oral
Bioavailability:<10% (due to first-
pass metabolis m)
Drug:Digoxin
Route:oral
Bioavailability:~70-80%
Drug:aspirin
Route:oral
Bioavailability:~50
Summary + Super Simple Trick🤓🤘:
Think of your body like a busy city 🏙️.
When a drug enters, it’s like a new guest arriving in the city.
👉 First, the city decides where to send the guest — some go to the kidney station 🚽 (urine), some to the liver gate 🍔 (bile), some leave through the lungs’ exit 🌬️ (exhalation), and a few sneak out through side doors like sweat and saliva 😅.
👉 How fast and how much of the guest reaches the city center (blood) depends on bioavailability — like how smooth the roads are 🚗. If the guest takes a direct flight (IV), they reach 100%. But if they come by a rough road (oral), traffic like enzymes and stomach acid slows them down!
Easy Trick to Remember Excretion & Bioavailability:
“KUB-L” → Think K-U-B-L like a short name:
K – Kidneys → drugs leave in urine
U – Urine pH matters → acidic/basic drugs excreted differently
B – Bile/Liver → drugs can go into intestines or reabsorbed
L – Lungs → gases and volatile drugs leave via breath
Bioavailability (F) → “How much reaches blood alive?”
Oral? Less (first-pass effect)
IV? 100%
Other routes? Depends on absorption
FAQs (Frequently asked questions)
1. What is elimination of a drug?
Elimination is the removal of a drug from the body, either as the unchanged drug or as its metabolites. It includes both metabolism and excretion.
👉 Example: Paracetamol is metabolized in the liver and then eliminated through urine.
2. What is excretion of a drug?
Excretion is the process of removing the unchanged drug and its metabolites from the body, mainly through the kidneys (urine), but also via bile, lungs, sweat, saliva, and breast milk.
👉 Example: Penicillin is excreted through urine.
3. What is bioavailability?
Bioavailability is the percentage of the drug that reaches the systemic circulation in its active form after administration.
👉 Example: IV drugs have 100% bioavailability, while oral drugs may have less due to first-pass metabolism.
4. What are the 4 types of pharmacokinetics?
The 4 main processes of pharmacokinetics are remembered by ADME:
A – Absorption
D – Distribution
M – Metabolism
E – Excretion
5. What is the difference between elimination and excretion of drugs?
Elimination = Metabolism + Excretion (overall removal of the drug from the body)
Excretion = Physical removal of the drug/metabolites through urine, bile, etc.
👉 Simply: Elimination is a broader term, while excretion is one part of elimination.
6. What are the major routes of drug excretion?
The main routes are:
Kidneys (urine) – major route
Liver (bile/feces)
Lungs (exhalation)
Minor routes: sweat, saliva, breast milk
👉 Example: Alcohol is excreted through urine and breath.
7. What factors affect drug excretion?
Excretion depends on:
Kidney function
Blood flow to organs
Drug properties (solubility, molecular size)
Urine pH and interactions with other drugs
8. How does urine pH affect drug excretion?
Acidic urine → increases excretion of basic drugs (e.g., amphetamines)
Alkaline urine → increases excretion of acidic drugs (e.g., aspirin)
Urine pH can be adjusted to speed up drug elimination in overdoses.
9. What are the types of bioavailability?
Absolute bioavailability: compares non-IV route with IV (100%)
Relative bioavailability: compares different non-IV formulations (e.g., tablet vs capsule)
10. How to calculate bioavailability?
Formula:
F = (AUC oral / AUC IV)×100)
11. Why is bioavailability important in medicine?
Ensures correct dosage for therapeutic effect
Helps in drug formulation (e.g., tablets vs injections)
Reduces side effects by optimizing drug levels in blood
12. What is first-pass metabolism?
The metabolism of a drug in the liver before it reaches systemic circulation
Reduces the amount of active drug available
👉 Example: Nitroglycerin has low oral bioavailability (~10%) due to first-pass metabolism.
13. How can bioavailability be increased?
Using sublingual, rectal, or inhalation routes to bypass the liver formulating prodrugs that convert into active drugs in the body using lipid-based formulations or nanotechnology to improve absorption
🔍For the basics, read🤝
For a smooth journey through pharmacokinetics, check Part 1 first:
Absorption, Distribution & Deposition.
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