further discussion about general pharmacology.

1. Mr. Mayur A. Haral
Department of
Pharmacology
Ishwar Deshmukh Institute
of Pharmacy, Digras 445203

2. Bioavailability
• Bioavailability is measurement of the rate and amount of therapeutically active drug that reach the systemic
circulation and is available at the site of action.
• If 100mg of drug is administrated orally and 80mg of this is absorbed unchanged, bioavailability is 0.8 or 80%
• Bioavailability is useful for determining quality of dosage forms in connection with influence of processing
factors, excipients, storage, stability, interaction & patients related factors.
• Bioavailability is compared or calculated by comparing plasma level of drug on oral administration with plasma
levels of drugs on intravenous administration.
Factors affecting Bioavailability
1. Physical state of drug 2. Particle Size
3. Solubility of Drug 4. Gastric Emptying Time.
5. Food & Drug Interaction 6. Route of Administration

3. • Physical state of drug:
Bioavailability is in reducing order in following physical state of the drug.
a) Liquids > Solids.
b) Solution > Suspension > Capsule > Tablet > Coated tablet.
c) Crystalloids > Colloids.
• Particle Size: Reduction in particle size of
drug increases the bioavailability.
• Stability of drug: Very hydrophilic drugs
have low bioavailability due to their inability
to cross lipid rich cell membrane and
hydrophobic drugs have more bioavailability.
• Food & Drug Interaction: Bioavailability
tetracycline is reduced if taken with milk
because it forms poorly absorbed complex
with calcium, liq. Paraffin decreases
bioavailability of fat soluble vitamins as it
emulsify the fats.
• Gastric Emptying Time: As duodenum has the
greatest capacity for the absorption of drug due to
the large surface area, gastric emptying time is
important factor.
Less gastric emptying time
Gastric contents are quickly available in
intestine
More Bioavailability

4. • Factors that influence gastric emptying rate are: a) Volume of meal b) Composition of meal
c) Viscosity of meal d) Temperature of meal
e) Gastro-intestinal pH f) Body temperature
g) Emotional state h) GIT disorders
All the above factors are affecting Bioavailability of drug.
• Route of Administration:
Bioavailability varies as per route of administration as
follows:
Route Bioavailability
Intravenous 100%
Intramuscular 75% to 100%
Subcutaneous 75%
Oral 5% to < 100%
Rectal 30% to < 100%
Inhalation 5% to < 100%

5. Distribution
• Drugs after administration are distributed widely in the body. Distribution of drugs means transport of drugs to
their targeted tissue i.e. site of action
• For drug distribution body fluids act as solvent and vehicle.
• Drugs are widely distributed in extracellular fluid, in blood, adipose tissue and body tissue.
• Drugs are mainly metabolized in liver, kidney, lungs, skin and placenta.

6. • The pharmacological agents, when administrated in a suitable dosage form, enter the blood
stream, get uniformly distributed in the body and then reach the site of action.
In this involve transport of drug molecules across the membrane of gastro-intestinal epithelium ,
blood brain barrier, placental membrane etc. this occur by following mechanism
• Drug when enter the vascular system, get distributed in various
tissues and body fluids. The ways which this process takes place are:
1) The drug may largely stick to walls of the vascular system.
2) Low molecular weight agents get distributed via the body water.
3) most of the pharmacological agents show un-uniform distribution.
4) Some agent are concentrated specifically in one/other tissue.
• The above processes are affected by following factors
1) Plasma protein binding.
2) Physicochemical characteristics
3) Routs of administration.
4) The presence of active transport system.
5) Specific barriers.

7. • Factors affecting drug Distribution:
1. Tissue Permeability of Drugs
a) Physicochemical Properties of drug like:
Molecular size, pKa, o/w Partition Coefficient
b) Physiological barriers to diffusion of drugs
2. Organ/tissue size and perfusion rate
3. Binding of drugs to tissue components.
a) Binding of drug to blood components
b) binding of drug to extra cellular components
4. Miscellaneous
Age
Pregnancy
Obesity
Diet
Disease states
Drug interaction

8. Metabolism/Biotransformation of drugs:
• Metabolism/Biotransformation means chemical alteration of the drug in the body.
• It is needed to render non polar (liquid soluble) compound polar (liquid insoluble) so that
they are not reabsorbed in the renal tubulars and are excreted.
• The absence of metabolism body will not be able to get rid of lipophilic substances and
they will become very long acting.
• The primary site for drug metabolism is liver. Other are - Kidney, Intestine, lungs, and
plasma.
Metabolism or biotransformation of drugs is the enzymatic conversion of drugs into
metabolites that are suitable for excretion from the body. It is an essential pharmacokinetic
process which convert lipid soluble and non-polar drug compound so that they are excreted
by various process.

9. Type of Metabolism/Biotransformation :
1. Inactivation:- Most drugs and their active metabolites are rendered inactive or less active. Eg.
Ibuprofen, paracetamol, lidocaine etc.
2. Active metabolite from an active drugs : Many drugs have been found to be properly converted to
one or more active metabolite. The effects observed are the SumTotal of that due to the parent drug
and it's active metabolite.
3. Activation of inactive drugs: Few drugs are inactive as such and need conversion in the body to
one or more active metabolites such a drug is called a prodrug. The prodrug may offer advantages
over the active form in being more stable having better bioavailability.
FACTORS AFFECTING DRUG METABOLISM:-
1. Age differences
2. Species and strain differences
3. Sex differences
4. Enzyme induction
5. Enzyme inhibition
6. Stereochemical Aspects of Drug metabolism