DRUG EXCRETION AND

ELIMINATION

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 DRUG EXCRETION
Excretion is the passage out of systemically absorbed drug.
Drugs and their metabolites are excreted in:

1. Urine Through the kidney. It is the most important

channel of excretion for majority of drugs.
e.g. acetazolamide, benzyl penicillin, dopamine,
pethidine, thiazides, histamine.
2. Faeces Apart from the unabsorbed fraction, most of the
drug present in faeces is derived from bile.
e.g. aluminium hydroxide, ferrous sulfate and rifampicin.

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 DRUG EXCRETION
3. Exhaled air Gases and volatile liquids (general
anaesthetics, alcohol) are eliminated by lungs,
irrespective of their lipid solubility.
4. Saliva and sweat These are of minor
importance for drug excretion. Lithium, pot.
iodide, rifampin and heavy metals are present
in these secretions in significant amounts.

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 DRUG EXCRETION
5. Milk The excretion of drug in milk is not
important for the mother, but the suckling
infant inadvertently receives the drug. Most
drugs enter the breast milk by passive
diffusion.
• e.g. ampicillin, aspirin, chlordiazepoxide,
coffee, diazepam, furosemide, morphine,
streptomycin etc.

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 KINETICS OF ELIMINATION
• The knowledge of kinetics of elimination of a
drug provides the basis for, as well as serves to
devise rational dosage regimens and to modify
them according to individual needs.
• There are three fundamental pharmacokinetic
parameters, viz. bioavailability (F), volume of
distribution (V) and clearance (CL)

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 BIOAVAILABILITY
• Bioavailability refers to the rate and extent of
absorption of a drug from a dosage form as
determined by its concentration-time curve in
blood or by its excretion in urine.
• It is a measure of the fraction (F ) of
administered dose of a drug that reaches the
systemic circulation in the unchanged form.

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APPARENT VOLUME OF DISTRIBUTION (V)

• Presuming that the body behaves as a single

homogeneous compartment with volume V
into which the drug gets immediately and
uniformly distributed
dose administered i.v.
V = ——————————
plasma concentration

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 CLEARANCE (CL)
• The clearance of a drug is the theoretical
volume of plasma from which the drug is
completely removed in unit time
• Clearance can be calculated as
CL = Rate of elimination/C
where C is the plasma concentration.

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 ORDER OF KINETICS
• Drugs usually follow two processes for their
phamacokinetic behaviour in the body.
• These are first order and zero order process.
First order:
• This is the most common process for many drugs. The
rate at which absorption, distribution, metabolism and
excretion occur are proportional to the concentration
of drugs
• i.e. constant fraction of this drug in the body
disappears in each equal interval of time.
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 ORDER OF KINETICS
Zero order kinetic:
• It is independent of the amount of drug present at the
particular sites of drug absorption or elimination.
• Few drugs follow this process e.g. ethanol, phenytoin.
• Here constant amount of the drug is eliminated in
each equal interval of time.
• On repeated administration of drug after certain stage
it goes on accumulating in the body and leads to toxic
reactions.

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 ORDER OF KINETICS
• Steady state plasma concentration:
When a drug dose is given repeatedly over a
given period, a steady state is eventually reached,
at which point the amount of drug absorbed is in
equilibrium with that eliminated from the body.
• Plasma half-life:
The Plasma half-life (t½) of a drug is the time
taken for its plasma concentration to be reduced
to half of its original value.
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 ORDER OF KINETICS
• Loading dose:
The loading dose is one or a series of doses that
may be given at the onset of therapy with the
aim of achieving the target concentration rapidly.
• Maintenance dose:
To maintain the chosen steady-state or target
concentration, the rate of drug administration is
adjusted such that the rate of input equals to rate
of loss.
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 REFERENCES
• K.D.Tripathi. Essentials of Medical Pharmacology,
JAYPEE Brothers Medical Publishers (P) Ltd, New Delhi.

• G. Brenner. Pharmacology. 1stt ed. Saunders:

Philadelphia. PA, 2000. ISBN 0-7216-7757-6

• M. J. Mycek, R. A. Harvey and P. C. Champe,

Lippincott’s Illustrated Reviews: Pharmacology,
Editors, J. B. Lippincott Company, Philadelphia, PA,
2000. ISBN 0-7817-2413-9

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THANK YOU