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By
Dr. G.SAILAJA,M.Pharm.Ph.D.,
Assoc. Professor,
Dept. of Pharmaceutics
“ Excretion is defined as the process where by drugs or
metabolites are irreversibly transferred from internal to
external environment through renal or non renal routes.”
Excretion of unchanged or intact drug is needed in
termination of its pharmacological action.
The principal organ of excretion are kidneys.
Agent that excreted in urine are :
1. water soluble 2.non volatile
3. small in molecular size(< 500 daltons.)
4. which are metabolized slowly 2
TYPES OF EXCRETION
RENAL EXCRETION : By Kidneys
NON RENAL EXCRETION
Biliary excretion.
Pulmonary excretion.
Salivary excretion.
Mammary excretion.
Skin / Dermal excretion.
Gastrointestinal excretion.
Genital excretion.
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•Functional unit of kidney in excretion is the
nephron
•Each kidney comprises of one million nephrons
•Each nephron is made up of
1. Glomerulus
2. Proximal tubule
3. Henle loop
4. Distal tubule
5. collecting tubule
URINARY EXCRETION PROCESS
•It includes
Glomerular filtration
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•Lipophilic drugs are reabsorbed
•Reabsorption of weak acids / weak bases
depends upon degree of ionisation
--------- Ph of the urine
--------Pka of drug
-------- urine flow rate
NEPHRON
FACTORS AFFECTING RENAL EXCRETION
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pH and pKa OF THE URINE :
It varies between 4.5 to 7.5
diet - carbohydrate – high alkaline pH
Protein - lower alkaline Ph
drug intake – sodium bicarbonate- alkaline ph
Ascorbic acid – acidic ph
Patho physiology of the patient- alkalosis – alkalization of urine
acidosis- acidification of urine
• IV infusion of sodium bicarbonate and ammonium chloride used in
treatment of acid base imbalance.
• Relative amount of ionized, unionized drug in the urine at
particular pH can be given by
“ HENDERSON-HESSELBACH” equation
HENDERSON-HESSELBACH EQUATION
For weak acids :
pH= pKa +log [ ionized ]
[unionized]
% of drug ionized = 10 (pH – pKa) X 100
1+10 (pH – pKa)
For weak base :
pH=pKa +log [unionized]/ionized
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• If R : concentration ratio of the drug in urine to
that in plasma then
• Ra= U = 1+ 10 ( ph urine- pka)
P 1+10 (ph plasma- pka)
Very weakly acidic drugs, non polardrugs (pka>8) and very weak
bases , non polar ( pka <6) are mostly unionised throughout the
entire range of urine ph – reabsorbed passively at all values of
urine ph.
• Rate of excretion is low and insensitive to urinary ph.
• Ex: phenytoin, propoxyphylline
A strongly acidic drug (pka<2.0) or a strongly basic drug
(pka>12.0) is completely ionized at all values of urine ph and
therefore not reabsorbed
• Rate of excretion is always high and insensitive to ph of urine
• Ex: cromoglycic acid, guanethidine
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BINDING CHARACTERISTICS OF THEDRUGS
• Clearance is inversely proportional to apparent vd
• Large vd drug is poorly excreted in urine
• Drugs that are bound to plasma proteins behave as
macromolecules and cannot be filtered through glomerulus
• Cl R = urine drug concentration urine flow rate
• plasma drug concentration
3
1
2
excretion
• Rate of
plasma concentration
BIOLOGICAL FACTORS :
• Age, sex, species, strain difference etc., alter the excretion
of the drug.
• Sex – Renal excretion is 10% lower in female than in males.
• Age – The renal function in newborn is 30-40 % less in
comparison to adults.
• Old age – The GFR is reduced and tubular function is
altered which results in slow excretion of drugs and
prolonged half lives.
BLOOD FLOW TO THE KIDNEY :
• Important in case of drug excreted by glomerular filteration
and those are actively secreted (more contact with the drug)
only.
• Increase the perfusion enhance the elimination.
URINE FLOW RATE :
Polar drug are not affected by urine pH hence not get
reabsorbed so unaffected by urine flow rate.
Only those drugs whose re absorption is pH sensitive Ex.
Weak acids and bases depend on urine flow rate.
Urine flow rate can be increased by forced diuresis by large
fluid intake or other diuretics.
Both urine ph control and forced diuresis used to treat
toxicity.
When drug was excreted by renal route only
Drug is absorbed passively from the renal tubules
Reabsorption is sensitive to ph
DRUG INTERACTIONS :
RENAL DYSFUNCTION
2 ) PULMONARY EXCRETION :
Gaseous and volatile substances such as general anesthetics
(Halothane) are absorbed through lungs by simple diffusion.
6 ) GASTROINTESTINAL EXCRETION :
Excretion of drugs through GIT usually occurs after parenteral
administration.
Water soluble and ionized form of weakly acidic and basic drugs are
excreted in GIT.
Example are nicotine and quinine are excreted in stomach.
Drugs excreted in GIT are reabsorbed into systemic circulation &
undergo recycling.
EXCRETION PATHWAYS, TRANSPORT
MECHANISMS & DRUG EXCRETED.
Excretory Mechanism Drug Excreted
route
Urine GF/ ATS/ ATR, PTR Free, hydrophilic, unchanged drugs/
metabolites of MW< 300
Bile Active secretion Hydrophilic, unchanged drugs/
metabolites/ conjugates of MW >500
Lung Passive diffusion Gaseous &volatile, blood & tissue
insoluble drugs
saliva Passive diffusion Free, unionized, lipophilic drugs. Some
Active transport polar drugs
Milk Passive diffusion Free, unionized, lipophilic drugs (basic)
Sweat Passive diffusion Free, unionized lipophilic drugs
Intestine Passive diffusion Water soluble. Ionized drugs
REFERENCES
Brahmankar M D., Jaiswal S B., Biopharmaceutics and
Pharmacokinetics A Treatise vallabh prakasan I edition 2002,
p.no;178-192.
Shrgel L., Wu-Pong S., Yu A B C., Applied Biopharmaceutics
& Pharmacokinetics V edition 2005,Mc Graw Hill
publication house p.no;131-159.
Venkateswarlu V., Biopharmaceutics and Pharmacokinetics II
edition 2008, PharmaMed Press, p.no;103-145.
Gibaldi M., Biopharmaceutics and Clinical Pharmacokinetics
IV edition 2006, PharmaMed Press,p.no; 203
Ali J., Khar R K., Ahuja A., A Text Book of
Biopharmaceutics and Pharmacokinetics , II edition 2005,
Birla Publication Pvt.Ltd, p.no;121-131.
THANK YOU …