Unit 1 PRINCIPLES OF

BASIC & CLINICAL

Part 4 Pharmacokinetics.

At the end of this chapter , You will be able to

 Explain the various aspects of clinical
pharmacokinetics
 What is clinical pharmacokinetics ?
& Why?
• Knowledge of kinetics applied ( In the clinical
situation) to improve the outcome of treatment.
• The knowledge derived is also used during the drug
development ( for optimum formulation) , to
determine the dose and frequency of dosing.
• Important in the management of emergency ,
especially when treated with drugs with narrow TI.
• Digoxin , Theophylline, some NS antibiotics
 Drug absorption after IV administration

•100 mg>>> 75
mg>>>10 mg ( In
the Biophase) .
•Serum level of drug
falls due to
metabolism and
subsequent
elimination etc •C max – Maximum concentration of the drug in the
serum ,
•T max - Time required to achieve this concentration
•AUC – AREA UNDER CURVE. Shows the
duration of the drug in the system
 CLINICAL PHARMACOKINETICS
Drug absorption
•When a drug is taken routinely
as treatment, the lowest
concentration just before the
next dose is called the Cmin or
Ctrough (trough level).

•After taking a drug, levels peak quickly then drop slowly as the drug is eliminated
(cleared from the body) – every drug has its own absorption curve.
•The highest concentration is called the Cmax.
•The total exposure to drug over the dosing period is call the Area Under the
Curve (AUC)
•The time taken to get to the highest concentration is called the Tmax
•The time taken to reduce the highest concentration by half (by 50%) is called
a drug’s ‘half-life’ or T½.
•It takes approximately 5 half-lives for a drug to be cleared to negligible levels,
but in theory, tiny quantities can be in the body for much longer.
 Drug absorption after multiple doses

•Each dose taken on time makes sure that the drug

stays above the lowest useful level (called
the Minimum Effective Concentration or MEC).
•Remember that all these results are averages.
•Some people absorb drugs more quickly or more
slowly than the average.
•Some people clear drugs more quickly or more
slowly than the average.
•These results are usually only calculated in blood
and blood levels do not always relate to how active
a drug is inside a cell.
 BIOAVAILABILITY ( f)
• Defined as the fraction of drug administered reaching
the systemic circulation as an intact Drug.
• BA depends on Route of drug administration and
drug formulations.
• BA for IV is 100%, other parenteral < 100%
• BA for ORAL < 100% due to variety of factors and
transport mechanism of transportation.
• Absolute BA : of a product when compared to IV
route.
• Relative BA: When compared b/w 2 different routes
of drug administration.
 BIOAVAILABILITY ( f)
• Example
 Propranolol : F= 100 ( IV route) and F =0.2 ( Oral )
 Digitalis : F =1 ( IV), app <1 ( as liquid) and -1 ( Oral)
 Clearance
• Describes the efficacy of irreversible elimination of
drug from the body.
• Defines as Volume of blood from which drug can
be completely removed/ unit time.
• Involves metabolism ( forming metabolite) and
elimination from the system.
• Drug >>> glucuronidation>>> said to be cleared
>> not removed from the system.
• Followed by excretion.
 VOLUME OF DISTRIBUTION
• Relates to concentration of drug measured in the blood to the
amount of drug in the body.
• Where is the drug?
• Refers to overall distribution of the drug and do not refer to
the actual volume. ( ex: say 40 L)
• Greater the volume of distribution,
 greater the disffusability of the drug.
 Drug is bound to / at EXTRAVASCULAR spaces.

• Eg: Vd =12 L represents extracellular distribution – unable

to penetrate the cell.
• Ex; Thiopental – a ultra short acting barbiturate has
higher volume of distribution – indicating that the drug is
distribute in the extravascular spaces.
 VOLUME OF DISTRIBUTION
IBUPROFEN AMIODARONE
• Vd is 0.14 L / kg in 70 kg • Vd = 60 L/ kg in 70 kg
person. person.
• Vd is 10.8 L /Kg >> shows • 60x70 = 4200 L / 70 kg
that drug is extensively person.
distributed equivalent, to • Suggests extensive
plasma volume. distribution through out the
• Not in the extravascular body ( Including the eye)
spaces.
 ORDERS of KINETICS
First Order Of Kinetics :
The rate of elimination of a drug is directly proportional to the
drug concentration.
It means a constant fraction of drug ( present in the body) is
eliminated / unit time.
Majority of the drugs follow first order kinetics.

Zero order kinetics : The rate of elimination of drug remains constant

irrespective of drug concentration.
Constant amount of drug is eliminated in unit time.

Plasma half life : Plasma half life of a drug is time taken for its plasma
concentration to be reduced to half of its original volume.