This document discusses various processes involved in the removal of drugs and their metabolites from the body. The major routes of excretion include renal, biliary, fecal, alveolar, and others like milk, skin, hair, sweat and saliva. Renal excretion depends on glomerular filtration, active tubular secretion, and passive tubular reabsorption. The molecular size, plasma protein binding, and renal blood flow influence the amount of drug excreted through glomerular filtration. Active tubular secretion is an energy-requiring process where drugs are secreted into the tubular lumen. Biliary excretion involves drugs being excreted in bile and sometimes undergoing enterohepatic circulation. Drug clearance

1. • Removal of Drug/ its metabolites from the body
(as unchanged / water soluble metabolites).
• Major routes: Renal , Biliary , Fecal , Alveolar
• Other : Milk, Skin , Hair , Sweat , Saliva
Excretion

2. 1. Renal Excretion:
e.g. Frusemide, Gentamicin, d-TC, digoxin etc)
• Amount of Drug / Metabolites excreted
(i.e. ultimately present in urine) depends on
following Processes:
• Net Renal Excretion (RE) = (GF + ATS) - PTR
Where, GF = Glomerular Filtration
ATS = Active Tubular Secretion
PTR = Passive Tubular Reabsorption

3. • 20% drug
• 3 Factors influence excretion:
1. Molecular size of the drug :
Glomerular capillaries have larger pores than usual,
therefore can filter out all non protein bound drugs
(Lipid soluble and insoluble).
If molecular size is < 20,000 (macro-molecular
substances).
e.g. Heparin, GF, Insulin, Dextran, etc are not
filtered.
Glomerular Filtration

4. 2. PLASMA PROTEIN BINDING (PPB) : excretion.
only free drugs can be filtered through glomerulus.
e.g. Warfarin = High PPB (98%), only 2% is excreted
through glomerulus.
3. RBF : blood flow to kidney faster removal of drug from
plasma.
GFR (N= 120 ml/min) in elderly and renal failure (due to no. of
glomeruli)

5. • Rest of 80% of drug passes on to the proximal tubule then
secreted into the tubular lumen.
• ‘Energy requiring’ carrier mediated active transport system.
• Cells of the proximal tubules actively secrete acids & bases by
two transport systems.
• Thus acidic drugs like penicillin, salicylic acid, probencid,
frusemide; basic drugs like amphetamine and histamine are so
excreted.
• Drugs may compete for the same transport system resulting in
prolongation of action of each other e.g. Penicillin & probenecid.
Active Tubular Secretion

6. 2 Independent renal transporters are operating at this level:
1. For ACIDIC Drugs (OAT=Organic Anion Transporter) e.g.
Captopril , Penicillin,etc
2. For BASIC Drugs (OCT=Organic Cation Transporter) e.g.
Cimetidine, Ranitidine, Metformin, Procainamide,
Nicotine,etc.
• Carrier system -non-specific, therefore drug having
similar physicochemical properties compete for the same
carrier system.

7. • e.g. Probenecid -organic acid has high affinity for tubular
OAT, therefore blocks the active transport of penicillin (β
lactam antibiotic). Thereby plasma t1/2 & effectiveness in
the Rx of certain infective diseases.

8. Passive diffusion of drug molecules can occur in
either direction in the renal tubules depending on :
1. Drug concentration
2. Lipid solubility
3. pH of urine
Strongly acidic & basic drug remain in ionized form
at any pH of urine & hence are excreted in urine.
Passive Tubular Reabsorption

9. Weakly acidic drugs
(Salicylates, Barbiturates
etc.)
in acidic urine
Remain mainly in
unionised form.
Reabsorbed in circulation.
If urine made alkaline
(Sod.bicarb/citrate)
• Weakly basic drugs
(Morphine, Amphetamine etc.)
in alkaline urine
Remain mainly in
unionised form.
Reabsorbed in circulation
If urine made acidic
(Vitamin C).

10. • If urine made alkaline
(sod.bicarb/citrate)
Get ionised
excreted easily
• Therapeutic regimen
treatment for
salicylate or
barbiturate poisoning.
• If urine made acidic
(vitamin C).
Get ionised
excreted easily.
• cannot use for
treatment because it
can cause ‘acidosis’ 
induce
rhabdomyolysis,
cardiotoxicity.
• Quartenary ammonium compounds & AMG’s  highly
polar not reabsorbed rather primarily excreted.

11. • Drugs eliminated through bile : Corticosteroids, Quinine
and Erythromycin.
After excretion in bile, drugs are reabsorbed back from
gut and are carried to liver. This cycle repeats and it is
called as enterohepatic circulation.
Benefits of enterohepatic circulation
- Increased duration of action of drug
- Acts as a reservoir of drug
Biliary Excretion

12. a) Orally ingested which are not absorbed through gut
e.g. MgSO4, Streptomycin, Neomycin, etc.
b) Drug excreted through bile but not reabsorbed from GIT.
e.g. Erythromycin, Corticosteroids etc.
Excreted through breath, irrespective of lipid solubility,
because excretion depends on their partial pressure in the
blood.
e.g. GA, NO, alcohol, paraldehyde, etc.
Why imp?: -It can cause unwanted effect in the
infant.
Faecal excretion
ALVEOLAR EXCRETION
Milk

13. • (Theoretical) volume of plasma from which the drug
is completely removed in unit time.
i.e. CL= Rate of elimination
Plasma conc.(C)
• The total ability of the body to clear a drug from
the plasma is renal clearance plus hepatic
clearance plus clearance from all other tissues.
CLEARANCE

14. • First order kinetics Constant fraction of the drug is
metabolized/eliminated per unit time.
• Most drugs follow 1st order kinetics and the rate of
metabolism/excretion is dependent on their concentration in the
body.
100ug/ml
1hr
50%
50 ug/ml
1hr
50%
25 ug/ml
1hr
50% 50%
12.5 ug/ml
1hr
6.2 ug/ml

15. • Zero order kinetics Constant amount of the drug present in the body is
metabolized/eliminated per unit time.
• The metabolic enzymes get saturated and hence with increase the dose
,the plasma drug level increases disproportionately resulting in toxicity
200ug/ml
1hr
50ug
150ug/ml 100ug/ml
1hr
50ug 50ug
50 ug/ml
1hr 1hr
50ug
0ug

16. First order kinetics:
• Rate of elimination is proportional to
plasma concentration
• Half life of drug is constant, even if
drug is administered at high dose.
Because high conc. of drug increases
clearance also
• Drug accumulation risk – low
• Drugs do not saturate the elimination
process
• Most of drugs follow 1st order kinetics
e.g. paracetamol, chloroquine etc.
Zero order kinetics:
• Rate of elimination is not proportional to plasma
concentration.
• Half life is not constant; initially, 200ug/ml to
100ug/ml in 2 hr,while at higher dose, 400ug/ml to
200ug/ml in 4hr.
• In zero order kinetics, half life is increased
because clearance decreases with increase
concentration of drug.
• Drug accumulation risk -high
• -Eg. Phenytoin, Warfarin, Alcohol

17. • PLASMA HALF-LIFE (t1/2 )-Time duration in which plasma conc.
of the drug falls by 50 % of the earlier value.
• Significance of plasma t1/2 : plasma t1/2 is necessary to know
the
- Duration of action of the drug
- Frequency of administration
- Time needed for attainment of SSCP - longer the t1/2
longer is the time needed to attain SSCP
- To calculate the loading and maintenance doses of the drug

18. Steady state plasma concentration(SSPC)
SSPC
When drug is given- conc. Gradually – achieves peak- then fall d.t.
Metabolism/excretion – but when drug is given again at constant interval- again
rise in conc.- after 7-8 half lives ,SSPC is achieved.
If very long t1/2 life of drug – long time taken to achieve SSPC- so loading
dose is given to achieve SSPC rapidly
Loading
dose