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PHARMACOKINETICS
BY: - J. Y. Burade
(Lecturer)
Dr. Rajendra Gode College of Pharmacy
Amravati
Content
Sr. No. Particular
01 Introduction
02 Absorption
03 Bioavailability
04 Distribution
05 Metabolism
06 Excretion
Introduction
• What body does to the drug ?
• DEF- -- Study of movement of drug through body (change in
concentration of drug from entry to its exit out of body).
Pharmacon – Drug Kinetics – Movement
• Also called ADME study .
A D M E
ABSORPTION
DISTRIBUTION METABOLISM
EXCRETION
D
O
L
O
How body reacts with drug?
Absorption
1) ABSORPTION –Movement of drug from route of administration into
systemic circulation (all the process before drug enters to systemic
circulation).
2) Drug transport across the membrane takes place either by passive or
active transport.
GETTING INTO
BODY
Weakly acidic drug
Unionised form
Better absorbed
from the stomach
in
Weakly basic drug
Unionised in
Better absorbed from the
intestine
in
Factors Affecting Absorption
Physical state
of drug
1. Liquids are better absorbed than solid.
2. Crystalloids are more readily absorbed than colloids.
3. Aqueous are more quickly absorbed than oily solutions
Particle size
1. Smaller particle size se surface area for absorption due to that
absorption rate is se.
Concentration 1. Higher concentration of drugs aids in better absorption of those
drugs.
Absorbing
surface
1. Absorption rate of gastrointestinal mucosa is more than pulmonary
endothelium of skin.
2. Absorption of drugs from highly vascular membrane will be rapid.
3. Larger the surface more is the absorption. Absorption from intestine is
more than stomach
Functional
integrity of GIT
pH of Drug
Formulation
1. Absorption of drug from the GIT may be effectively sed by se
in peristaltic activity.
1. Acidic drugs absorbed from the stomach. E.g., Salicylates and
barbiturates.
2. Basic drugs absorbed from the intestine. E.g., Pethidine and
ephedrine.
1. Calcium and magnesium ions reduced the absorption of
tetracycline.
2. Low degree of ionisation, high lipid/water partition coefficient
of non-ionised form and smaller molecular size of water soluble
substance , all favours rapid absorption.
Bioavailability
It is the fraction of a drug that reaches systemic circulation
100
mg
50
mg
50%
Bioavailability
Factors affecting bioavailability
Bioavailability
Concentration
Particle size
Physical state of
drugs
Dissolution rate
Absorbing surface
Functional integrity
of GIT
pH of drug
Gastric emptying
time
Degree of
ionization
Molecular
weight
Lipid solubility
First pass
metabolism
Disease state of
the gut
Formulation
Distribution
After the drug reaches into the blood circulation it may be distributed
to various tissue and organs.
Vd= Volume of distribution
Vd =
𝐓𝐨𝐭𝐚𝐥 𝐚𝐦𝐨𝐮𝐧𝐭 𝐨𝐟 𝐝𝐫𝐮𝐠 𝐢𝐧 𝐛𝐨𝐝𝐲
𝐂𝐨𝐧𝐜𝐞𝐧𝐭𝐫𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐝𝐫𝐮𝐠 𝐢𝐧 𝐩𝐥𝐚𝐬𝐦𝐚
Factors affecting distribution
Physiological
Factors
Physiochemical
Properties of Drug
1. Cardiac output
2. Regional blood flow
3. Capillary permeability
4. Tissue volume
5. Special tissue characteristics
such as blood brain barrier
1. Binding to plasma proteins
2. Binding to other tissues like fat,
liver, bone etc
3. Affinity for tissue constituents
4. Tissue redistribution
Metabolism
• Also called biotransformation
• 2 types of metabolism: - a. Non synthetic reaction (phase I reaction)
i. Oxidation
ii. Reduction
iii. Hydrolysis
iv. Cyclilization
v. Decyclilization
b. Synthetic reaction (Phase II reaction) conjugation reactions
i. Glucoronide conjugation
ii. Acetylation
iii. Methylation
iv. Sulfate conjugation
v. Glycine conjugation
vi. Glutathion conjugation
Factors
affecting
drug
metabolism
Genetic
Factor Environmental
Factor
Nutritional
status
Presence of liver
diseases
Presence of
kidney
diseases
Drug-food
interaction
Metabolising
enzyme
inhibition
Metabolising
enzyme
induction
Genetic
factors
1. Acetylation of drugs show genetic polymorphism.
2. The individual fall clearly under fast and slow acetylation.
Nutritional
status of
individual
Environmental
factors
Diseases
state of
individual
1. Drugs or environmental toxins can induce hepatic microsomal enzyme oxidising
system or cyp450 resulting into rapid metabolism and elimination of drug.
2. The environmental pollutants like pesticides can induce metabolism.
1. Malnutrition in children and in malnourished elderly, the drug oxidation rate is
severely decreased.
2. Whereas high protein diet act as metabolising enzyme inducers.
3. Alcohol consumption have both enzyme induction effect at low dose and at high
dose metabolic inhibition effect.
1. Liver being major site of drug metabolism, in patients with liver diseases (cirrhosis)
metabolism of drug is severely reduced, resulting in drug toxicity.
2. Similarly in patients with kidney disease; se elimination of drug metabolites is
observed.
Drug – drug
interaction
Drug food
interaction
Simultaneous administration of two drugs causing interaction may
show:- Inhibitory effect or stimulatory effect
Tyramine present in cheese, bananas may not metabolized by MAO if
MAO- inhibitors is given and a severe hypertension crisis may result.
Excretion
• Elimination from body
Organs
involved in
drug
excretion
Kidneys Lungs
Intestines
Bile
Skin
Saliva & Milk
Remember:- Many
drugs are eliminated
by the kidney
without being. Renal
disease can therefore
slow excretion of
some drugs
REFERENCE
• Dr. Yadav A. V. , Mrs. Dubal A. S. , Pharmacology, Nirali
Prakashan,first edition, June 2022, Page no. :-1.1-1.20
• Tripathi K. D., Essentials of medical pharmacology, Jaypee brothers
medical,8th Edition, 2018 Page no. 01-22.
THANK YOU !

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PHARMACOKINETICS.pptx

  • 1. PHARMACOKINETICS BY: - J. Y. Burade (Lecturer) Dr. Rajendra Gode College of Pharmacy Amravati
  • 2. Content Sr. No. Particular 01 Introduction 02 Absorption 03 Bioavailability 04 Distribution 05 Metabolism 06 Excretion
  • 3. Introduction • What body does to the drug ? • DEF- -- Study of movement of drug through body (change in concentration of drug from entry to its exit out of body). Pharmacon – Drug Kinetics – Movement • Also called ADME study . A D M E ABSORPTION DISTRIBUTION METABOLISM EXCRETION D O L O How body reacts with drug?
  • 4. Absorption 1) ABSORPTION –Movement of drug from route of administration into systemic circulation (all the process before drug enters to systemic circulation). 2) Drug transport across the membrane takes place either by passive or active transport. GETTING INTO BODY Weakly acidic drug Unionised form Better absorbed from the stomach in Weakly basic drug Unionised in Better absorbed from the intestine in
  • 5. Factors Affecting Absorption Physical state of drug 1. Liquids are better absorbed than solid. 2. Crystalloids are more readily absorbed than colloids. 3. Aqueous are more quickly absorbed than oily solutions Particle size 1. Smaller particle size se surface area for absorption due to that absorption rate is se. Concentration 1. Higher concentration of drugs aids in better absorption of those drugs. Absorbing surface 1. Absorption rate of gastrointestinal mucosa is more than pulmonary endothelium of skin. 2. Absorption of drugs from highly vascular membrane will be rapid. 3. Larger the surface more is the absorption. Absorption from intestine is more than stomach
  • 6. Functional integrity of GIT pH of Drug Formulation 1. Absorption of drug from the GIT may be effectively sed by se in peristaltic activity. 1. Acidic drugs absorbed from the stomach. E.g., Salicylates and barbiturates. 2. Basic drugs absorbed from the intestine. E.g., Pethidine and ephedrine. 1. Calcium and magnesium ions reduced the absorption of tetracycline. 2. Low degree of ionisation, high lipid/water partition coefficient of non-ionised form and smaller molecular size of water soluble substance , all favours rapid absorption.
  • 7. Bioavailability It is the fraction of a drug that reaches systemic circulation 100 mg 50 mg 50% Bioavailability
  • 8. Factors affecting bioavailability Bioavailability Concentration Particle size Physical state of drugs Dissolution rate Absorbing surface Functional integrity of GIT pH of drug Gastric emptying time Degree of ionization Molecular weight Lipid solubility First pass metabolism Disease state of the gut Formulation
  • 9. Distribution After the drug reaches into the blood circulation it may be distributed to various tissue and organs. Vd= Volume of distribution Vd = 𝐓𝐨𝐭𝐚𝐥 𝐚𝐦𝐨𝐮𝐧𝐭 𝐨𝐟 𝐝𝐫𝐮𝐠 𝐢𝐧 𝐛𝐨𝐝𝐲 𝐂𝐨𝐧𝐜𝐞𝐧𝐭𝐫𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐝𝐫𝐮𝐠 𝐢𝐧 𝐩𝐥𝐚𝐬𝐦𝐚
  • 10. Factors affecting distribution Physiological Factors Physiochemical Properties of Drug 1. Cardiac output 2. Regional blood flow 3. Capillary permeability 4. Tissue volume 5. Special tissue characteristics such as blood brain barrier 1. Binding to plasma proteins 2. Binding to other tissues like fat, liver, bone etc 3. Affinity for tissue constituents 4. Tissue redistribution
  • 11. Metabolism • Also called biotransformation • 2 types of metabolism: - a. Non synthetic reaction (phase I reaction) i. Oxidation ii. Reduction iii. Hydrolysis iv. Cyclilization v. Decyclilization b. Synthetic reaction (Phase II reaction) conjugation reactions i. Glucoronide conjugation ii. Acetylation iii. Methylation iv. Sulfate conjugation v. Glycine conjugation vi. Glutathion conjugation
  • 12. Factors affecting drug metabolism Genetic Factor Environmental Factor Nutritional status Presence of liver diseases Presence of kidney diseases Drug-food interaction Metabolising enzyme inhibition Metabolising enzyme induction
  • 13. Genetic factors 1. Acetylation of drugs show genetic polymorphism. 2. The individual fall clearly under fast and slow acetylation. Nutritional status of individual Environmental factors Diseases state of individual 1. Drugs or environmental toxins can induce hepatic microsomal enzyme oxidising system or cyp450 resulting into rapid metabolism and elimination of drug. 2. The environmental pollutants like pesticides can induce metabolism. 1. Malnutrition in children and in malnourished elderly, the drug oxidation rate is severely decreased. 2. Whereas high protein diet act as metabolising enzyme inducers. 3. Alcohol consumption have both enzyme induction effect at low dose and at high dose metabolic inhibition effect. 1. Liver being major site of drug metabolism, in patients with liver diseases (cirrhosis) metabolism of drug is severely reduced, resulting in drug toxicity. 2. Similarly in patients with kidney disease; se elimination of drug metabolites is observed.
  • 14. Drug – drug interaction Drug food interaction Simultaneous administration of two drugs causing interaction may show:- Inhibitory effect or stimulatory effect Tyramine present in cheese, bananas may not metabolized by MAO if MAO- inhibitors is given and a severe hypertension crisis may result.
  • 15. Excretion • Elimination from body Organs involved in drug excretion Kidneys Lungs Intestines Bile Skin Saliva & Milk Remember:- Many drugs are eliminated by the kidney without being. Renal disease can therefore slow excretion of some drugs
  • 16. REFERENCE • Dr. Yadav A. V. , Mrs. Dubal A. S. , Pharmacology, Nirali Prakashan,first edition, June 2022, Page no. :-1.1-1.20 • Tripathi K. D., Essentials of medical pharmacology, Jaypee brothers medical,8th Edition, 2018 Page no. 01-22.