This document provides an overview of pharmacokinetics principles including absorption, distribution, metabolism, and elimination of drugs. It discusses how pharmacokinetics is important for ensuring therapeutic drug levels while avoiding toxicity. Key points covered include the mechanisms and factors affecting drug absorption and bioavailability, the distribution of drugs to tissues, the metabolism and excretion of drugs, and how clinical pharmacokinetics applies these principles to optimize drug therapy for individual patients.

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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