ADVANCED BIOPHARMACEUTICS AND PHARMACOKINETICS- EXCRETION OF DRUGS VIA DIFFERENT ROUTES

1. NAME:STEFFI THOMAS
M.PHARM,2ND SEM
DEPARTMENT OF PHARMACY
B.U.,BHOPAL

2.  It’s a process whereby drugs/metabolites are
irreversibly transferred from the internal to the
external environment
OR
 It is the passage out of systemically absorbed drug.
 Principal organs involved,
-kidneys RENAL EXCRETION
-lungs(pulmonary)
-biliary system
-intestines NON-RENAL EXCRETION
-saliva
-milk(mammary)

3.  Kidney is the primary organ of removal for most
drugs especially for those that are water soluble
and not volatile.
 The three principle processes that determine the
urinary excretion of a drug
1.Glomerular filtration,
2.Tubular secretion and
3.Tubular reabsorption (mostly passive back-
diffusion)

5.  The ultrastructure of the glomerular capillary wall
is such that it permits a high degree of fluid
filtration while restricting the passage of
compounds having relatively large molecular
weights.
 The selective filtration is important in that it
prevents the filtration of plasma proteins
(e.g.,albumin) that are important for maintaining
the plasma volume.
 Several factors,including molecular size,charge
and shape influence the glomerular filtration of
large molecules.

6.  As the ultrafiltrate is formed, any drug that is free
in the plasma water, that is, not bound to plasma
proteins or the formed elements in the blood (e.g.,
red blood cells), will be filtered as a result of the
driving force provided by cardiac pumping.
 All unbound drugs will be filtered as long as their
molecular size, charge and shape are not
excessively large.
 Compounds with 20Aº to 42Aºmay undergo
glomerular filtration.
 GFR normally is 120ml/min.
 GFR declines progressively after the age of 50 and
also low in renal failure

7.  Many drugs which don’t enter into GF but do so
by tubule secretion which mainly occurs in
proximal tubules.
 It is carrier mediated process which require energy
for transportation of compounds against against
the concentration gradient.
 2 secretion mechanisms are identified:
-system for secretion of organic acids/anions
e.g. penicillins, salicylates etc.
-system for organic bases/cations
e.g. morphine, mecamylamine,hexamethonium

8.  These active secretory systems are important in
drug excretion because charged anions and cations
are often strongly bound to plasma proteins and
therefore are not readily available for excretion by
filtration.
 Active secretory systems can rapidly and
efficiently remove many protein-bound drugs from
the blood and transport them into tubular fluid.

10.  Some substances filtered at the glomerulus are
reabsorbed by passive diffusion and depends on
the lipid solubility and ionization of drug at the
existing urinary pH.
 So lipid soluble drugs filtered from GF but 99% of
the drug is reabsorbed but non-lipid soluble and
highly ionized drugs are unable to do so
 Active reabsorption is particularly important for
endogenous substances, such as ions, glucose and
amino acids although a small number of drugs also
may be actively reabsorbed

11.  The rate of urinary drug excretion will depend on
the drug’s volume of distribution, its degree of
protein binding, and the following renal factors:
-glomerular filtration rate
-extent of active tubular secretion of the compound
-possibly extent of active tubular reabsorption

12.  Bile juice is secreted by the hepatic cells of the
liver (steady flow-0.5 to 1 ml/min) is important for
the digestion and absorption of fats.
 Greater the polarity better the excretion so
metabolites are more excreted than parent
compound.
 Generally larger molecules (MW>300) are
eliminated by bile.
 Some drugs which are excreted as glucuronides are
hydrolysed by intestinal/ bacterial enzymes to the
parent drug which are reabsorbed (enterohepatic
cycling).

15.  Extensive enterohepatic cycling may be partly
responsible for a drug’s long persistence in the
body.
 Orally administered activated charcoal and/ or
anion exchange resins have been used clinically to
interrupt enterohepatic cycling and trap drugs in
the gastrointestinal tract.

16.  Gases and other volatile substances are eliminated
by lungs, irrespective to their lipid solubility.
 Alveolar transfer of the gas/vapour depends on its
partial pressure in the blood.
 E.g. alcohol, general anaesthetics

17.  The pH of saliva varies from 5.8 to 8.4.
 Unionized lipid-soluble form of the drugs are
excreted passively.
 Thus, the bitter after taste in the mouth of a patient
is an indication of drug excretion.
 Substances excreted into saliva are usually
swallowed and therefore there is the same as that
of orally administered.
 E.g. caffeine, metronidazole, alcohol etc.

18.  Milk consists of lactic secretions which is rich in
fats and proteins.
 Excretion of drug in milk is important as it gains
entry in breast feeding infants.
 pH of milk varies from 6.4 to 7.6. Free unionized
and lipid soluble drugs diffuse passively.
 Highly plasma bound drug like Diazepam is less
secreted in milk.
 Amount of drug excreted in milk is less than 1%
and fraction consumed by infant is too less to
produce toxic effects .Some potent drugs like
barbiturates and morphine may induce toxicity.

19.  Drugs secreted through skin via sweat follows pH
partition hypothesis. Excretion of drugs through skin
may lead to urticaria and dermatitis. Compounds
like benzoic acid, salicylic acid, alcohol and heavy
metals like lead, mercury and arsenic are excreted in
sweat.