Lecture 02

1. LECTURE 02: PHARMACOKINETICS (LADMER;
LIBERATION, ABSORPTION, DISTRIBUTION,
ELIMINATION AND RESPONSE).
What is Pharmacokinetics:
How the human body act on the drug?
Pharmacokinetics is the quantitative study and characterization of the time course of drug absorption,
distribution, metabolism and excretion (ADME) and it is determined by measuring a plasma profile.
Pharmacokinetic properties of particular drug is important to determine the route of administration, dose, onset
of action, peak action time, duration of action and frequency of dosing.
In contrast, pharmacodynamics is the study of the biochemical and physiological effects of the drug on the
body, or the relationship between drug concentration at the site of action and the resulting effect or we can say
what the drug does to the body.
Pharmacokinetics can be used in the clinical setting to enhance the safe and effective therapeutic management
of individual patients and is termed clinical pharmacokinetics.

2. Absorption:
Is the transfer of a drug from its site of administration
to the blood stream. Most of drug absorbed by the
way of passive transport. I.V administration has no
absorption. Drug which are unionized, low polarity
and higher lipid solubility are easy to permeate
membrane. Drug which are ionized, high polarity
and low lipid solubility are difficult to permeate
membrane.
distribution :
A dynamic equilibrium normally exists between the
concentration of the drug in the blood plasma and
the concentration of the drug at its site(s) of action.
The extend of distribution of drug depends on its
lipid solubility, ionization at physiological
Ph(dependent on pKa),extend of binding to plasma
and tissues protein and differences in regional blood
flow,diseases like CHE,uremiac, Cirrhosis.

3. Metabolism/Elimination:
The drug can either be enzymatically cleaved or biochemically
transformed,in which case it is said to have been metabolized, or be
excreted unchanged. The study and characterization of the time
course of drug absorption, distribution,metabolism and excretion
(ADME) is termed pharmacokinetics.Chemical alteration of the drug in
the body, mean to convert non polar lipid soluble compounds to polar
lipid insoluble compound to avoid reabsorption in renal tubules. Most
of hydrophilic drug are less biotransformed and excreted unchanged
e.g. streptomycin, neostigmine and pancuronium etc.
Biotransformation is required for protection of body from toxic
metabolites.
Excretion:
It is a transport procedure which the prototype drug or parent drug or
its metabolic products are excreted through excretion organs or
secretion rogan.The routes of drug excretion are kindney, Biliary
excretion, sweat and saliva,milk and pulmonary (respiration). Fig. 18.1
illustrates some of the factors that can
influence the concentration of the drug in the blood plasma and also at
its site(s) of action. Biopharmaceutics is concerned with the first stage
– getting the drug from its site of administration into the bloodstream or
systemic circulation.

5. Pharmacokinetic or ADME Process by Different dosage forms

6. THE BIOPHARMACEUTICS CLASSIFICATION SYSTEM
Most of the failures in drug development can be traced to poor biopharmaceutical properties, namely, poor
dissolution or poor permeability, Gordon Amidon introduced the Biopharmaceutics Classification System
(BCS) [1]. According to the BCS, orally administered drugs are divided into four classes on the basis of their
solubility and permeability characteristics [2)
1. Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic
drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability.
Pharmaceut Res 1995;12:41320.
2. FDA. The Biopharmaceutics Classification System (BCS) Guidance. ,http://www.fda.
gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm128219.
htm.; 2009.

7. Concept of biopharmaceutics:
• in the same type of dosage form by different routes of administration (e.g. an
aqueous solution of a given drug administered by the oral and intramuscular
routes);
• by the same routes of administration but in different types of dosage form
(e.g. a tablet, a
hard gelatin capsule and an aqueous suspension administered by the peroral
route); or
• in the same type of dosage form by the same route of administration but with
different formulations of the dosage form (e.g. different formulations of an oral
aqueous suspension).
Variability in the bioavailability exhibited by a given drug from different
formulations of the same type of dosage form, or from different types of dosage
forms, or by different routes of administration, can cause the plasma
concentration of the drug to be too high, and therefore cause side effects, or
too low,and therefore the drug will be ineffective. Fig. 18.2 shows the plasma
concentration–time curve following
a single oral dose of a drug, indicating the parameters associated with a
therapeutic effect. The therapeutic window is the drug concentrations which are
above the minimum effective concentration and below the maximum safe
concentration.

8. Poor biopharmaceutical properties may result in:
• poor and variable bioavailability;
• difficulties in toxicological evaluation;
• difficulties with bioequivalence of formulations;
• multiple daily dosing;
• the requirement for a nonconventional delivery system;
• long and costly development times; and
• high cost of products.
Summary:
A thorough understanding of the biopharmaceutical properties of a candidate drug is
important both in the discovery setting, where potential drug candidates are being
considered, and in the development setting,
where it is important to anticipate formulation and manufacturing problems. The
influence of variability and bioequivalence issues on clinical results must be studied
to provide assurance to the regulatory authorities as to the robustness and quality of
the drug substance and drug product.