“FIX ME BABY

ONE MORE TIME”

PROCESS OF REMOVING A DRUG
AND ITS METABOLITES

INETXCRO
MAJOR ORGAN EXCRETING
DRUGS

YDIKEN
AGE, SEX, AND SPECIES
C A N A LT E R E X C R E T I O N O F
DRUGS

OOIGILBCAL
RSTOCFA
WHEN INCREASED THE
PERFUSION ENHANCES THE
E L I M I N AT I O N

L BOD O F W OL O T
HET KNYEID
R ESULT IN ALTERATION OF BINDING
C HARACTERISTICS, URINE PH, FORCED
D IURESIS ETC. WOULD ALTER RENAL
C LEARANCE OF DRUGS

GDUR
NTECTONIRAI
A CHEMICAL PROPERTY REFERRING
T O H O W A D R U G C A N E A S I LY O R
H A R D LY E X C RET E T H E D R U G

B I S O I T L U LY
DEFINED AS THE VOLUME OF
PL ASMA THAT IS CLEARED OF
DRUG PER UNIT OF TIME
THROUGH THE KIDNEY

NLEAR
CRLAEANCE
WHAT IS DRUG
EXCRETION?
Excretion is the process of removing
a drug and its metabolites from the
body or irreversible transfer from
internal to external environment
through renal or non renal route.
HUMANS EXCRETE WASTE PRODUCTS
THROUGH?
Kidneys (Renal Excretion)
Bile (Biliary Excretion)
Lungs (Pulmonary Excretion)
Saliva (Salivary Excretion)
Milk (Mammary Excretion)
Sweat (Skin Excretion)
>Most drugs, particularly water-soluble drugs and their metabolites, are
eliminated largely by the kidneys in urine.
 RENAL
EXCRETION
• - drugs are eliminated
from the body primarily
by the kidneys.

• The principal renal

mechanisms:
• 1. Glomerular filtration
• 2. Active tubular
secretion
• 3. Active tubular
reabsorption
FACTORS AFFECTING RENAL EXCRETION
 Urine pH and pKa.
 Blood flow to the kidneys.
 Physicochemical properties of drug.
 Distribution and Binding characteristic of drug.
 Biological factors.
 Urine flow rate.
 Drug interactions.
 Disease states.
I) PH AND PKA OF THE URINE :
• It varies between 4.5 to 7.5 depending on the diet (e.g. meat can
cause a more acidic urine) or food rich in carbohydrate ↑ pH
• Many drugs are either weak bases or acids and therefore the pH of
the filtrate can greatly influence the extent of tubular re-absorption
for many drugs.
• When urine is acidic, weak acid drugs tend to be reabsorbed.
Alternatively when urine is more alkaline, weak bases are more
extensively reabsorbed.
• Excretion of some drugs can be increased by suitable adjustment of
urine pH e.g. pentobarbital (a weak acid) overdose may be treated
by making the urine more alkaline with sodium bicarbonate
injection.
• Acetazolamide(carbonic anhydrase inhibitor) and antacids
produce alkaline urine, while ascorbic acid makes it acidic
• A polar & ionized drug will be poorly reabsorbed passively &
excreted rapidly.
Reabsorption is also affected by the lipid solubility of drug ;
• an ionized but lipophilic drug will be reabsorbed while an
• unionized but polar one will be excreted.
The toxicity due to overdose of the drug whose excretion is
sensitive to pH change can be treated by acidification or
alkalinisation of the urine.
II) PHYSICOCHEMICAL PROPERTIES OF DRUG :

Molecular size
Drugs with Mol.wt <300 are excreted in kidney.
Mol.wt 300 to 500 Dalton are excreted both
through urine and bile
III) BINDING CHARACTERISTICS OF THE
DRUGS :
Drugs that are bound to plasma proteins behave as
macromolecules and cannot be filtered through glomerulus.
Only unbound or free drug appear in glomerular filtrate.
Protein bound drug has long half lives.
IV) 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 excretion 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
V) BLOOD FLOW TO THE KIDNEY :

• Important in case of drug excreted by glomerular

filtration and those are actively secreted only.
• Increase the perfusion enhance the elimination.
VI) 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 reabsorption 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.
VII)DRUG INTERACTIONS :
• Any drug interaction that result in alteration of
binding characteristics, renal blood flow, active
secretion, urine pH, and forced diuresis would alter
renal clearance of drug.
• Alkalinization of urine with citrates and bicarbonates
promote excretion of acidic drugs.
VIII) DISEASE STATE :
• RENAL DYSFUNCTION
– Greatly cause the elimination of drugs those are primarily excreted
by kidney.
– Some of the causes of renal failure are hypertention, Diabetes,
hypovolemiya(low blood supply to kidney), heavy metals.
• UREMIA(azotemia)
– Characterized by Impaired GF , accumulation of fluids & protein
metabolites(NH3),resulting in drug accumulation and increased
toxicity.
NON-RENAL
ROUTES
Drug elimination in the urine
To be extensively excreted in urine, a drug or metabolite must be water
soluble and must not be bound too tightly to proteins in the bloodstream.
The acidity of urine, which is affected by diet, drugs, and kidney disorders, can
affect the rate at which the kidneys excrete some drugs.

The kidneys’ ability to excrete drugs also depends on:

• Urine flow
• Blood flow through the kidneys
• The condition of the kidneys

A major characteristic of compounds excreted in urine is that they are

polarized and water-soluble. Drugs that are lipid soluble are not
readily removed by the kidneys and require hepatic metabolism to
increase their water solubility for possible urinary excretion.
SALIVARY EXCRETION

MAMMARY EXCRETION
SWEAT EXCRETION
References
http://www.msdmanuals.com/professional/clinical-
pharmacology/pharmacokinetics/drug-excretion
https://www.msdmanuals.com/home/drugs/administration-and-kinetics-of-
drugs/drug-elimination
http://accesspharmacy.mhmedical.com/content.aspx?bookid=513&sectionid=41
488024
http://watcut.uwaterloo.ca/webnotes/Pharmacology/kineticsRenalElimination.h
tml
http://www.columbia.edu/itc/gsas/g9600/2004/GrazianoReadings/Drugabs.pdf
https://www.slideshare.net/bknanjwade/hepatic-clearance-and-
eliminationhttps://www.slideshare.net/bknanjwade/hepatic-clearance-and-
elimination
https://www.youtube.com/watch?v=uB27m6oPhlo