Drugs are eliminated from the body through metabolism and excretion. The major routes of excretion include renal (kidney), biliary (bile), fecal, alveolar (lungs), and minor routes like skin, saliva, sweat, hair, and milk. The kidney is the most common route and filters drugs through glomerular filtration while tubular secretion and reabsorption also influence renal excretion. Certain drugs can interact by competing for tubular secretion. Biliary excretion and enterohepatic circulation recirculate some drugs through the liver and intestines. Adjusting urine pH can enhance the excretion of acidic or alkaline drugs. Accumulation may occur if drugs rely on renal excretion and

1. Drug Excretion
Dr Naser Ashraf Tadvi
Associate Professor

2. Drug elimination
Metabolism
(Biotransformation)
Excretion+

3. Biotransformation
• “ Chemical alteration of the
drug in the body.”
Converts non polar
(lipid soluble)
substances
In to polar (lipid
insoluble)
substance
No reabsorption in
renal tubules
Excretion in urine

4. Excretion
• Excretion is the passage out of
systemically administered drugs.
• Removal of the drug and its metabolite
from body is known as drug excretion

5. Routes of drug excretion
Major
• Renal
• Biliary
• Fecal
• Alveolar
Minor
• Skin
• Saliva
• Sweat
• Hair
• Milk

6. KIDNEY
• Most common for majority of the drugs.
• Excretes water soluble substances.
• Renal excretion determined by 3 processes:
– Glomerular filtration
– Tubular reabsorption
– Tubular secretion
• NET RENAL EXCRETION = (Glomerular filtration +
Tubular secretion ) – (tubular reabsorption )

7. Glomerular Filtration
• Glomerular capillaries have large pores.
• All FREE drugs (lipid soluble or insoluble) are filtered
through it.
• Glomerular filtration depend upon …
• Molecular size
• Plasma protein binding
• Renal blood flow.
• Normal GFR is 120 ml/min

8. Tubular reabsorption
• Occurs by passive diffusion and depends on
– Lipid solubility
– pKa of drug
– pH of urine
• pH of urine
– pH of urine is Acidic so generally weakly acidic drugs have
more chance of reabsorption
– Sodium bicarbonate used in Salicylate and barbiturate
poisoning to alkalinize urine
– Ascorbic acid can be used to ↑ excretion of Morphine

9. Tubular secretion
• Energy requiring carrier mediated active
transport
– OAT and OCT at proximal tubules.
– P-gp and MRP2 are located in the luminal
membrane of proximal tubular cells.
– ORGANIC ACID TRANSPORT (OAT) :
• Penicillin, probenecid, uric acid, salicylates,
indomethacin
– ORGANIC BASE TRANSPORT (OCT) :
• Morphine, quinidine, Procaine, Thiazides, furosemide

10. Drug interactions due to competition of
tubular secretion
• Probenecid
– Organic acid which has high affinity for the tubular OATP.
– Blocks the active transport of both penicillin and uric acid.
• Aspirin ↓ tubular secretion of methotrexate
• Quinidine inhibits p-glycoprotein and ↓ renal
and biliary clearance of digoxin

11. Penicillin is
exogenous
substance
Primarily undergoes
tubular secretion
so excreted
Probenecid
prevents this
RETAINED IN THE
BODY.
Uric acid is
endogenous
substance
Primarily undergoes
tubular reabsorption
so retained
Probenecid
prevents this
EXCRETED FROM THE
BODY.

12. Renal Elimination can enhanced by..
• Diuretics which increases the urine flow.
• Adjusting the pH of urine. How ?

13. Biliary excretion and enterohepatic
circulation
• Liver cells also transport various drugs and
endogenous substances like bilirubin from
plasma to bile using OATP and OCT
• Relatively larger Mol. weight drugs > 300
eliminated in bile
• Most of free drug in gut, including which is
released by deconjugation of glucuronides by
enteric bacteria are reabsorbed by Entero
hepatic circulation

14. Enterohepatic circulation
Enterohepatic
circulation
Drug enters
intestine
Absorbed in
portal blood
Reaches
liver
Taken by
hepatocytes
Excreted in
bile
Major fraction
gets excreted
Minor
fraction
reenters
circulation
So
increase
in
bioavailab
ility

15. Drugs undergoing enterohepatic
circulation
• Ampicillin
• Rifampicin
• Estrogen
• Morphine
• Doxycycline
• Cefoperazone

16. Faecal excretion
• Orally administered drugs that are
unabsorbed → excreted in feces
• Example
– streptomycin, neomycin, cholestyramine.

17. • Some drugs are expelled in expired air.
• Volatile General anaesthetics
• Alcohol
• Paraldehyde It is important from
medico legal
perspective because
presence of alcohol in
breath stamps that a
person has jumped
legal boundary !!!
Only 5 % of alcohol is
excreted in expired air. So
not important from
pharmacological or medical
point of view.
Entry through
inspiration
Exit through
expiration !!!
Alveolar excretion

18. Skin, Sweat, Saliva, Hair
• Skin:
o Arsenic and heavy metals like mercury gets
excreted in skin.
o Griseofulvin secreted through keratin precursor
cells
• Hair follicles: Arsenic, iodides, mercury salts
• Saliva: Iodine, potassium iodide, lithium,
phenytoin
• Sweat: Rifampicin, Amines, urea derivatives

19. Milk
• Most drugs enter breast milk by passive diffusion
• More lipid soluble and less protein bound drugs are
better concentrated in milk.
• “Basic drugs”are more concentrated in it as pH of
milk is acidic 6.8 -7.0
Drug
administered to
mother
Enters breast
milk
Reaches breast
feeding infant
May produce
effect on infant

20. Drugs in lactation
• Total amount of drug reaching infant through
milk is small and majority drugs have no
significant effect on infant.
• In infants → slower elimination → cumulation
may occur when baby receives it with frequent
breast feeding.
• Drugs should be administered only when
indicated and safe drugs should be used
• Safe drugs: Antacids, iron salts, paracetamol,
insulin, salbutamol , cephalosporin

21. Examples of drugs contraindicated in
lactation
• Radioactive iodine administered to mother →
reach the infant in breast milk → fetal goitre.
• Avoid chloramphenicol, tetracycline,
sulfonamides.
• Ergotamine → may cause ergotism.
• Chloroquine for rheumatoid arthritis → retinal
damage in infant.
• Cytotoxic drugs are absolutely contraindicated.

22. • If a drug is acidic in nature
• If a drug is alkaline in nature
• Some drugs are excreted unchanged in urine….so
in case of renal failure…
• Drugs, metabolites and toxins are excreted in the
urine →
How excretion pattern affects the therapeutic
effect…….
Its excretion can be
enhanced by
alkalinizing it.
Its excretion can be
enhanced by
acidifying it.
It is accumulated in
the body and
produces ADR.
So frequently
produces
nephrotoxicity