Pharmacokinetics of drugs is the study of (ADME) Absorption, Distribution, Metabolims, and Excretion. Pharmacokinetics is all about understanding how drugs move, change, and leave the body. This is one of the basic unit of pharmacology, to understand the subject pharmacology. This ppt will be use for MBBS, Nursing and Pharmacy students.

1. Pharmacokinetics
Akash Agnihotri
Department of Pharmacology
Amrita School of Medicine, Faridabad
Pharmacokinetics by Akash Agnihotri 1

2. Overview
Overview of PK-PD
Absorption- Plasma membrane, Mechanisms of drug transport
Bioavailability
Distribution
Metabolism- Phase-I, Phase-II
Excretion
Pharmacokinetics by Akash Agnihotri 2

3. Drug + Excipients
Drug in dosage form
Drug release and dissolution
Drug in systemic circulation
Extravascular Tissues
(Tissue at the site of action)
Pharmacological Response
Therapeutic/Toxic effects
PHARMACEUTICS FORMULATION
Oral administration
ABSORPTION
Disposition
DISTRIBUTION
Metabolism
&
Excretion
ELIMINATION
PHARMACOKINETICS
PHARMACODYNAMICS
THERAPEUTICS
Parenteral
Administration
Pharmacokinetics by Akash Agnihotri 3
Overview of
Pharmacokinetics-
Pharmacodynamics

4. Pharmacokinetics and Pharmacodynamics
• What the body does to the body
• Movement of drug within the body
• Includes the process of ADME
Pharmacokinetics
• What drug does to body
• Study of drugs, their mechanism of action,
pharmacological actions, and their adverse
effects
Pharmacodynamics
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5. Pharmacokinetics
• Study of Absorption, Distribution, Metabolism, and Excretion
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ADME
kADME
Kinetics Movement
Drug
Absorption
How will it get in?
Distribution
Where will it go?
Metabolism
How is it broken down?
Excretion
How does it leave?
Liver

6. Absorption
• Movement of drug from its site of administration into the blood stream or
central compartment
Pharmacokinetics by Akash Agnihotri 6
For Solid dosage form
Absorption first requires dissolution of tablet/Capsule
Liberating drugs

7. Plasma Membrane
7
Fluid Mosaic Model (Singer and Nicolson, 1972)
2 Types of pore-
- 10nm
- 50-70nm
Pores provide channel-
Water, ions & dissolved
solutes (Urea) may
move
(Pratt & Tylor 1990)
Hydrophobic tails
Hydrophilic Heads
Phospholipid
Bilayer
Regulates the movement of
molecules, including drugs,
between the inside of a cell
and the outside environment.
Pharmacokinetics by Akash Agnihotri

8. Mechanisms of Drug Transport
8
Passive
Diffusion
Carrier
mediated
Transport Vesicular
Transport
Pore
(Convective)
Transport Ion Pair
Formation
• Facilitated Diffusion
• Active Transport
• Primary
• Secondary
• Carrier mediated
intestinal Transport
• Pinocytosis
• Phagocytosis
1
2
3
4
5
Pharmacokinetics by Akash Agnihotri

9. Passive Diffusion
• Nonionic diffusion (90% drugs)
• Molecules spontaneously diffuse from a region of higher
concentration to a lower concentration
• Driving force- Solute’s Concentration (Electrochemical) gradient
• No external energy is required
9
Rate of Transfer= Flux
Pharmacokinetics by Akash Agnihotri

10. Passive Diffusion
• Best Expressed by- Fick’s law of diffusion (Adolf Fick)
• According to law- Drug molecules diffuse from a region of high drug
concentration to a region of low drug concentration
10
dQ
dt
=
DAK
h
(CGI - Cp)
Surface area (A) Diffusion rate Thickness(h) Diffusion rate
Lipid solubility Diffusion rate Molecular weight Diffusion rate

11. Carrier mediated Transport- Mechanism
11
• Carrier binds reversibly with solute molecule
• Made complex
• Travel across membrane to other side
• Dissociated and discharge drug
• Carrier return to its original site
Pharmacokinetics by Akash Agnihotri

12. Active Transport
12
• Drug transported from a region of lower to one of higher concentration
• Against concentration gradient
• Uphill transport (Energy is required)
• Driven by hydrolysis of adenosine triphosphate (ATP)
• Can be inhibited by metabolic poisoning that interfere with energy
production (e.g, Fluoride, cyanide and dinitrophenol)
• 5-fluorouracil (Lipid insoluble drug)- Absorbed by GI
Pharmacokinetics by Akash Agnihotri

13. Factors affecting absorption
• Effect of pH on drug absorption
• Blood flow to the absorption site
• Total surface area available for absorption
• Contact time at the absorption surface
• Expression of p-glycoprotein (Efflux transporter)
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14. Factors affecting absorption
Effect of pH on drug absorption:
• Most drugs are either weak acids or weak bases
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A drug passes through membranes
more readily if it is uncharged
When medium is same, drugs
can cross the membrane
Gastric pH= Acidic
Acidic drugs are more likely to be absorbed in
stomach, because of unionized form
e.g., Aspirin (acidic), morphine, atropine
(Basic)

15. Factors affecting absorption
• Effect of pH on drug absorption
• Blood flow to the absorption site
• Intestine absorbed more than stomach
• Total surface area available for absorption
• Intestine surface area 1000-fold that of stomach (microvilli)
• Contact time at the absorption surface
• Drug moves through GI very fast-not well absorbed drug
• Drug taken with a meal is generally absorbed more slowly
• Expression of p-glycoprotein
• It’s a transmembrane protein, responsible for transportation of drugs
• Expressed in liver, kidney, placenta, and intestine
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Physical factors:
• Particle size
• Presence of other drug
• Route of
administration

16. Bioavailability
• It is the fraction of administered drug that reaches the systemic
circulation in the unchanged form
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100 molecules of drugs
20 Molecules not absorbed
Excreted in feces as
such
Rest 80 Molecules will be
absorbed and go to liver
Absorption
=80%
Systemic circulation
30 M broken
50% molecule available
to produce action
This fraction is known
as Bioavailablity

17. First Pass Metabolism
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First pass metabolism or Presystemic elimination:
When a drug is absorbed from the GI tract, it enters the
portal circulation before entering the systemic circulation
Note: First-pass metabolism by the intestine or liver limits the efficacy of
many oral medications.
For example, more than 90% of nitroglycerin is cleared during first-pass
metabolism.
Hence, it is primarily administered via the sublingual or transdermal, or
intravenous route.

18. Distribution
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19. Distribution
Once absorbed into the bloodstream, a drug is distributed to all organs via
circulating blood
• A drug will have an effect once it reaches its site of action (e.g receptors)
• But may get bound to plasma proteins, or
• May accumulate in various storage sites, or
• May enter into tissues (not involved in primary action)
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20. • Movement of drug between the one compartment & the other
• Reversible transfer of a drug between the blood and extra vascular
fluids and tissues of body (for example, fat, muscle, and brain tissue)
• Predominantly a passive process - driving force is concentration
gradient between the blood and extravascular tissues
Drug distribution
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21. • Permeation of free or unbound drug into interstitial / extracellular fluid
• Permeation of drug present in extracellular fluid into intracellular fluid
(rate limiting step)
Steps in drug distribution
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22. Factor affecting distribution
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Physicochemical
properties of
drugs
• Molecular size
• Degree of ionization
(Unionized/Ionized)
• Lipid solubility
(Partition coefficient)
Physiological
Barriers
• Blood brain barrier
• Blood placental barrier
• Blood CSF barrier
• Simple capillary endothelial barrier
• Simple cell membrane barrier

23. Blood-Brain Barrier (BBB)
Only lipid soluble unionized drug can cross BBB
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24. • A solute may enter to brain via
1} Passive diffusion through the lipoidal barrier
2} Active transport of essential nutrients like sugars and amino acids
 As a rule only lipid soluble, nonionized form of drug penetrate more
easily to brain as compared to water-soluble ionized form of drug
 Can cross: Volatile anesthetics, ultra short acting barbiturates, narcotic
analgesic, dopamine precursors and sympathomimetics
 Can’t cross: Dopamine, serotonin, streptomycin, quaternary substances
Blood-Brain Barrier (BBB)
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25. • Inflammatory conditions (meningitis, viral infection of brain, heat stress)
alter permeability of BBB
• Example- Penicillins readily cross the BBB during meningitis
Blood-Brain Barrier (BBB)
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26. • Maternal & fetal blood vessels are separated by a number of tissue
layers made of fetal trophoblast , basement membrane & endothelium
–placental barrier
• Drugs having molecular size less than 1000 D and moderate lipid
solubility cross the placental barrier
• Dextran and Insulin, cannot cross placental barrier
Blood placental barrier
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27. Blood placental barrier
• Drugs that can cross Blood-Placental barrier:
• Ethanol, sulfonamides, barbiturates, gaseous anesthetics, steroids, narcotics,
anticonvulsants etc.
• Teratogenicity - Fetal abnormality caused by administration of drugs
during pregnancy
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28. • Also known as Apparent volume of distribution, is used to quantify the
distribution of a drug between plasma and the rest of the body after
oral or parenteral dosing
• All parts of the body equilibrated with the drug do not have equal
concentration
Volume of distribution
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29. • Volume of Distribution can be calculated by:
Amount of drug in body
Plasma drug concentration
• If 500 mg of drug reaches circulation…(total amount of drug)
• And if plasma concentration is 0.5 mg/ml
• Vd will be 500/0.5 = 1000 ml
• Which means we require 1000 ml of fluid to accommodate total 500 mg
of drug at concentration of 0.5 mg/ml
Vd =
Volume of distribution
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30. Metabolism
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31. Metabolism
Drug
(Lipophilic)
Metabolite
(Polar)
Enzy
me
Body
Excretion
Pharmacokinetics by Akash Agnihotri 31

32. Metabolism / Biotransformation
• Conversion from one chemical form to another
• Metabolism of lipid-soluble drugs to water-soluble structures is
needed for effective renal elimination
• Pharmacologic inactivation of drug:
• Phenytoin------------p-Hydroxy phenytoin
• Active drug to active metabolite:
• Digitoxin---------------Digoxin
• Activation of inactive drug (Prodrug):
• Aspirin------------------Salicylic acid
Primary site for drug metabolism- Liver, kidney, intestine, lungs, and plasma
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33. Metabolism: Phase-I & Phase-II
Biotransformation
Phase-I (Non-synthetic)
• Oxidation
• Hydroxylation, dealkylation,
deamination
• Reduction
• Hydrolysis
• Cyclization
• Decyclization
Phase-II (Synthetic/Conjugation)
• Glucuronide conjugation
• Glycine conjugation
• Glutathione conjugation
• Sulfate conjugation
• Acetylation
• Methylation
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34. Phase-I reactions
• Oxidation: addition of oxygen/negative charged radical or removal of
hydrogen
• Mostly carried out by group of monooxygenases in the liver
• Enzyme responsible for metabolism in liver:
Smooth ER
Cytochrome P450
Inducible
All Phase-I and only
glucuronidation
Location:
Main Enzyme:
Inducibility:
Metabolism:
Cytoplasm, mitochondria
Esterases, amidases
Non-Inducible
Phase-I- MAO & alcohol dehydrogenase
Phase-II except glucuronidation
Microsomal Enzyme Non-microsomal Enzyme
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35. Phase-I reactions
• Cytochrome p-450
Examples of drugs that are substrates of
P450 isoenzyme
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36. Phase-I Reaction
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37. Phase-II reactions
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38. Factor affecting metabolism
• Genetics influence whether a person can metabolize drugs at a quicker
or slower rate
• Age: Affect the performance of the liver;
• Elderly have a lesser liver function and may metabolize drugs more
slowly, increasing the risk of intolerability
• Newborns or infants have immature liver performance and may
necessitate unique dosing consideration
• Drug interactions can result in decreased drug metabolism via enzyme
inhibition or increased metabolism by enzyme induction
Pharmacokinetics by Akash Agnihotri 38

39. Excretion
Pharmacokinetics by Akash Agnihotri 39

40. Excretion
• Excretion is defined as the process where by drugs or metabolites are
irreversibly transferred from internal to external environment through
renal or non renal route
• Excretion of unchanged or intact drug is needed in termination of its
pharmacological action
The principle organ of excretion are kidneys
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41. Types of excretion
• Renal: Urine
• Faeces (Unabsorbed Drugs)
• Exhaled air
• Saliva and Sweat
• Milk
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42. Renal Elimination of Drug
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1. Glomerular Filtration
Free drug (not bound to albumin) flows
through the capillary slits into the
Bowman space as part of the glomerular
filtrate
2. Proximal Tubule Secretion
3. Distal Tubular Reabsorption

43. Types of excretion
• Renal: Urine: Paracetamol, Penicillin, Digoxin
• Faeces (Unabsorbed Drugs): Streptomycin, Neomycin
• Exhaled air: Volatile general anesthetics, Alcohol,
• Saliva and Sweat: Lithium, Metoclopramide, Rifampicin
• Milk: Caffeine, Acetylsalicylic acid, Morphine, Barbiturates
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44. Clearance & Half-Life (t1/2)
Clearance is the volume of plasma from which the drug is
completely removed per unit time
The amount eliminated is proportional to the concentration of
the drug in the blood stream
Half-life is the time required for the body to eliminate one-half
(50%) the amount of drug in the body
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45. Summary
• Pharmacokinetics: Kinetics of ADME
• Absorption: Movement of drug form site of adms to blood
• Drug transport: Passive diffusion (Conc gradient, Active transport (need
energy)
• Factor affecting absorption (pH, Blood flow, Surface area etc)
• Distribution: Movement of drug
• Only Unionized and Lipid soluble drug can cross the Barriers
• Metabolism: Conversion from one chemical form to another (Enzyme -
CYP450)
• Excretion: Removal of drug from body
Pharmacokinetics by Akash Agnihotri 45

46. References
• Textbook of Pharmacology, Pathology & Genetics for Nurses-I, 2nd edition
by Suresh Sharma
• Principles of pharmacology, 4th edition by H. L. Sharma & K .K. Sharma;
2023
• Essentials of Medical Pharmacology, 9th edition by KD Tripathi; 2024
• Biopharmaceutics and pharmacokinetics: A treatise, by Brahmankar DM,
Jaiswal SB; 2005
• Lippincott illustrated reviews pharmacology, 2nd SA edition by Sangeeta
Sharma; 2022
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47. Thank You
Pharmacokinetics by Akash Agnihotri 47