ppt

1. 1
By:
Assist lect. Muhanad
Rabaty
Pharmacy department
8th theoretical lecture
Principles
of
Pharmacoki
netics

2. Introduction
 Pharmacokinetics ; involves the study of absorption,
distribution, metabolism (biotransformation) and drug
excretion over time.
-- refers on how the body acts on the drug
-
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3. The question could be asked-why bother
about Pharmacokinetics ??????
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 To prevent, cure or control various disease states
adequate drug doses must be
delivered to the target tissues.
so that therapeutic yet NON – toxic levels
are obtained

4.  Too much of a drug will result into toxic effects &
too little will not result into the desired therapeutic
effects.
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5. CONT…
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 Monitor medications with a narrow therapeutic
index
 Decrease the risk of adverse effects while
maximizing pharmacologic response of
medications

6. 11/30/2016
Pharmacokinetic paths cont..
Drug & metabolites in urine, feces, or bile
Drug at the site ofAdministration
1 .ABSORPTION
(INPUT)
Drug in plasma
2. DISTRIBUTION
drug in tissues
3. METABOLISM
metabolites in tissues
4. ELIMINATION
(OUTPUT)

7. 1. Absorption of drugs
Absorption
Movement of drug from site of
administration to the systemic
circulation.
Route and site of administration
affect
 Rate and
 Extent of absorption
IV delivery – absorption is
complete
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8. Mechanisms of drug absorption
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There are 4 mechanisms by which drug molecules cross the
cell membrane:
 Passive diffusion
 Facilitated diffusion
 Active transport
 Bulk transport mechanisms

9. Bioavailability
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 The bioavailability of a drug is the fraction of the
dose administered which is absorbed and reaches
the systemic circulation.
 Bioavailability of drug injected i.v. is 100%, but is
frequently lower after oral ingestion,
 because:
🞑 The drug may be incompletely absorbed
🞑 The absorbed drug may undergo first pass metabolism
in intestinal wall and/or liver or be excreted in bile.
 For non I.V.: ranges from 0-100% (0 – 1)

10. First-Pass Metabolism
 Drug ⇒Oral administration ⇒G.I.T. ⇒ Portal
circulation ⇒Liver ( First pass metabolism ) ⇒
Systemic Circulation
 Decreases Bioavailability
 Decreases Therapeutic Response
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11. 1. Physicochemical properties of the drug
– Molecular shape (Physical state)
– Particle size
– Lipid solubility and unionized form of drug
– Disintegration and dissolution time
-Formulation
2. Route of drug administration
3. pH and ionization
4. Presence of other drugs
5. Patient conditions
eg. - Disease condition
– Presence or absence of food … affect absorption from the GI
Factors Affecting DrugAbsorption and Bioavailability

12. - Is a random movement drug molecules out of the systemic
circulation/ into the different body tissues
– Involves the delivery of drugs from the blood in to the target sites
2. DISTRIBUTION OF DRUGS

13. Factors Affecting Distribution of
Drugs
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1- Physicochemical properties of drugs
• Lipid solubility of the drug
• Degree of plasma protein.
2- Physiological factors
• Rate of blood flow
3- Presence of barriers
• BBB (blood brain barrier)

14. Drug - plasma protein binding
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 After entering the blood stream, drugs exist in two
forms [plasma protein bound & unbound form].
 Bound drugs are pharmacologically INACTIVE,
only the FREE, UNBOUND drug can act on target
sites in the tissues.

15. CONT…
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 The major plasma proteins that bind drugs are
– Albumin
– α-acid glycoprotein
– Lipoproteins
– Globulin

16. 3. Metabolism of Drugs
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The liver is the principal(The major site) organ for
drug metabolism.
Drugs are often eliminated by biotransformation and
or excretion into the URINE OR BILE.

17. cont…
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 Chemical alteration of the drug in the body.
 Aim: to convert non-polar lipid soluble compounds
to polar lipid insoluble compounds to avoid
reabsorption in renal tubules.
 Biotransformation is required for protection of
body from toxic metabolites

18. Results of Biotransformation
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1. Active drug and its metabolite to inactive.
2. Active drug to active.
3. Inactive drug to active/enhanced activity
(prodrug)
4. No toxic or less toxic drug to toxic metabolites.

19. Drug Excretion
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 The passage out of a systemically absorbed drug from the
body in the form of metabolites or unchanged drug
 Main Routes of Excretion
 Renal excretion (major organ)
 Hepatobiliary excretion
 Pulmonary excretion (for volatile/gaseous anaesthetics)
 Minor Routes of Excretion
 Saliva, sweat, milk, tears

20. Clinical pharmacokinetics
⚫Clinical Pharmacokinetics is the application of
the pharmacokinetic principles, using drug
concentration and pharmacodynamic criteria
to optimize drug therapy in individual
patient.

21. APPLYING PHARMACOKINETIC
PRINCIPLES
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 By using
1. Aloading dose in one or a series of doses that may
be given at the onset of therapy with the aim of
achieving the target concentration rapidly.
 loading dose = desired concentration * VD

22. Cont…
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2. Maintenance dose- is a dose administered to
maintain the target concentration of a drug. The
dose is equivalent to the excreted amount.
 DM = DL*(1- e-K*T)
3. Drug Half-Life—Time required for amount of drug
in the body/plasma conc. to decrease by 50%.

23. Cont…
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4. Clearance: The clearance (CL) of a drug is the
theoretical volume of plasma from which drug is
completely removed in unit time
- is fraction of the apparent volume of distribution from
which drug is removed in unit time.

24. 5. Volume of distribution (Vd)
Relates the amount of drug in the body to the concentration of
drug in blood or plasma.
-- Vd = [D]/[C]
» [D] = total concentration of the drug in the body
» [C] = concentration of the drug in the plasma

25. Thank
you