The document discusses the absorption and bioavailability of drugs, emphasizing factors influencing their extent of absorption through various routes. It explains how drug form, particle size, and physiological conditions can affect drug dissolution and absorption rates, as well as the concept of first-pass metabolism. Additionally, it highlights pharmacogenetic influences on bioavailability and presents questions regarding drug properties and administration routes.

1. Moderater- Dr Biswadeep Das
Additional Professor
Department of Pharmacology
AIIMS, Rishikesh
Presenter- Akash Agnihotri
M.Sc. Medical Pharmacology

2. •
For Solid dosage form
Absorption first requires dissolution of tablet/Capsule
Liberating drugs

3. From mouth- Saliva pH is slightly acidic, but pH of stimulated saliva
(with sublingual drugs) reaches 7.4
Hence, lipid-soluble, basic or neutral drugs can absorbed
from this site
From stomach- Acidic pH, Hence, lipid-soluble, basic or neutral drugs
can absorbed from this site
After absorption they pass through hepatic portal
system before going to systemic circulation –
hence chances of first-pass metabolism are increased

4. From intestine- pH is alkaline, e.g, morphine
From large intestine or colon-
• pH alkaline
• From external haemorrhoidal vein, major amount of drug goes
directly to systemic circulation, hence minimal first-pass effect

5. • When injected i.v. are completely absorbed and rapidly distributed
as they reach bloodstream directly without crossing any membrane
• Intramuscular and subcutaneous injections usually occurs by Passive
diffusion
• The extent of absorption from highest to lowest is:-
Intravenous Intramuscular Subcutaneous

6. • Lipid-soluble drugs when given in a vaporized form – general
anaesthetics
• Aqueous solution spray- Salbutamol
• Spray of suspended microfined particles- Disodium cromoglycate
Are absorbed by simple diffusion from pulmonary epithelium and mucous
membrane of trachea and lungs
• Absorption is rapid because large surface area
• First –pass metabolism is avoided

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8. • Fractional extent to which an administered dose of drug reaches its
site of action or a biological fluid (usually the systemic circulation)
from which the drug has access to its site of action
• Fraction of a dose F that is absorbed and escapes first-pass elimination
measures the drug’s bioavailability
F =
Quantity of drug reaching systemic circulation
Quantity of drug administered
thus, 0 < F ≤ 1

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15. •
ER =
CLliver
Q
Where Q is the hepatic blood flow, normally about 90 L/h in a person weighing 70 kg.

16. •
F = f X (1-ER)

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20. Fig: Rate and Extent of absorption in drug therapy

21. From the plasma concentration-time curves
Three important characteristics are noted and compared
1. Peak plasma concentration (Cmax)
2. Time to attain the peak plasma concentration (tmax)
3. Area Under Curve (AUC)

22. Peak plasma concentration (Cmax) :
• Peak plasma concentration that gives an indication whether the drug is sufficiently
absorbed systemically to provide a therapeutic response
• The extent of bioavailability can be determined by following equation:
F =
[AUC]oral Div
[AUC]iv Doral
Where D stands for dose administered

23. Time to attain the peak plasma concentration (tmax)
• The peak time that gives an indication of the rate of absorption

24. Area Under Curve (AUC)
• Reflects the extent of absorption
• It denotes total amount of drug absorbed into circulation during a specified period

25. Area Under Curve (AUC)
• AUC is expressed in units of mg-hr/ml
• Can be calculated by several methods
1. Planimeter- An instrument for mechanically measuring the area of plane figures
Degree of error is high due to instrumental & human error

26. Area Under Curve (AUC)
• Can be calculated by several methods:
2. Cut and weigh method- Means to cut out the area under the entire curve on
rectilinear graph paper and to weigh it on an analytical
balance
3. Counting the Square: Total no. of squares enclosed in the curve is counted.
Area of each square determined using relationship:
AREA=(height) (width)

27. Drug Bioavailability (%) =
AUC (oral)
AUC (IV)
X 100

28. Broadly classified as:
A) Pharmaceutical factors
B) Pharmacological factors

29. A. Pharmaceutical factors:
1. Particle Size:
• Rate at which a drug is dissolved can be increased by increasing its
surface area by decreasing its particle size. e.g- Microfined aspirin
2. Salt Form:
• Rate at which a particular salt dissolves differs from its parent compound.
Salts of weakly acidic drugs are highly water soluble, free acidic drugs is
precipitated from these salts is micro crystalline form, which has a faster
dissolution rate and increases bioavailability
Tolbutamide sodium and phenytoin sodium have better bioavailability than tolbutamide and phenytoin (free drug)

30. A. Pharmaceutical factors:
3. Crystal Forms:
• Rate of absorption and bioavailability of a drug also depends on its
crystalline form
• Because amorphous forms dissolve faster compared to crystalline forms,
because no energy is needed to break up the crystalline lattice, thus
increasing bioavailability
e.g, Amorphous chloramphenicol palmitate have faster dissolution and better
bioavailability than their crystalline forms

31. A. Pharmaceutical factors:
4. Water of hydration:
• If water molecules are already present in a crystal structure, tendency
of crystal to attract additional water to initiate dissolution process is
reduced, compared to anhydrous forms
e.g, Anhydrous form of caffeine, theophylline and ampicillin have better
bioavailability than hydrous forms

32. A. Pharmaceutical factors:
5. Nature of Excipients and Adjuvants:
• These pharmacologically inert substances , (e.g starch, lactose, calcium
sulfate, gum) which are added as filling material or as binding agents,
have tremendous effects on bioavailability of drugs
• Some of these excipients are wetting agents, which enhance solvent
penetration and ensures faster dissolution and in turn absorption

33. A. Pharmaceutical factors:
6. Degree of Ionisation
• Non-ionised, lipid soluble drugs are better absorbed, increasing their
bioavailability, compared to strongly acidic or strongly basic drugs or
highly ionised drugs
e.g, Streptomycin, Neostigmine, Acetylcholine

34. A. Pharmacological factors:
1. Gastric Emptying and Gastrointestinal Motility:
• Factors that accelerate gastric emptying increases the bioavailability
because drug is exposed to larger surface area of small intestine
Gastric emptying promoted by – Fasting, anxiety, hyperthyroidism
Gastric emptying retarded by- Atropine, imipramine and chlorpromazine

35. A. Pharmacological factors:
2. Gastrointestinal Diseases
• Many gastrointestinal diseases affect drug absorption, outcome of
Coeliac disease is complex, it increases absorption of cephalexin,
whereas reduces of amoxycillin
• In case of Crohn’s disease, there is disproportionate absorption of
individual components of cotrimoxazole, increases absorption of
sulfamethoxazole, decreases of trimethoprim

36. A. Pharmacological factors:
3. Food and Other Substances
• In general, GI absorption rate is reduced after ingestion of food, although
it has no effect on extent of absorption
• Both rate and extent of absorption of certain antibiotics like rifampicin is
reduced after meals
• Absorption of tetracyclines is reduced if taken with milk because it forms
poorly absorbed complexes with calcium
• Vit. C increases absorption of iron because it keeps it in it’s ferrous form

37. A. Pharmacological factors:
4. Drug-Drug Interactions
• Drug-drug interactions can cause difference in bioavailability
• Liquid paraffin decreases the bioavailability of fat soluble vitamins as it
emulsifies fat
• Antacids reduces bioavailability of tetracyclines because it forms chelated
complex

38. A. Pharmacological factors:
5. Pharmacogenetic Factors
• Large difference in bioavailability often occurs among humans due to
pharmacogenetic reasons
• Slow and fast acetylators show increased and decreased bioavailability of
isoniazid respectively

39. Q:1 Which of the following types of drugs will have maximum oral
bioavailability?
A. Drugs with high first-pass metabolism
B. Highly hydrophilic drugs
C. Largely hydrophobic, yet soluble in aqueous solutions
D. Chemically unstable drugs

40. Q:2 Which route of drug administration is most likely to lead to the
first-pass effect?
a) Sublingual
b) Oral
c) Intravenous
d) Intramuscular

41. Q:3 Bioavailability differences among oral formulations of
a drug are most likely to occur if the drug:
A. Is freely water soluble
B. Is completely absorbed
C. Is incompletely absorbed
D. Undergoes little first-pass metabolism

42. 1.
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3.