PHARMACOKINETICS
Pharmacokinetics is defined as the kinetics of drug absorption, distribution, metabolism and
excretion (ADME) and their relationship with the pharmacological, therapeutic or toxicological
response in man and animals.
Pharmacokinetic models
Models are used to describe changes in drug concentration in the body with time.
Model is a hypothesis that employs mathematical terms to concisely describe quantitative
relationships of drug(s) (w.r.t time) throughout the body and compute meaningful
pharmacokinetic parameters.
Compartmental Models
Assumptions
Compartment is not a real physiologic or anatomic region but a fictitious or virtual one
and considered as a tissue or group of tissues that have similar drug distribution
characteristics (similar blood flow and affinity).
The body is represented as a series of compartments arranged either in series or parallel
to each other, that communicate reversibly with each other.
Within each compartment, the drug is considered to be rapidly and uniformly distributed
i.e. the compartment is well-stirred.
Types of compartmental models
Depending upon arrangement of compartments
1. Mammillary model
2.Catenary model.
Depending upon number of compartments assumed
1.One-compartment or one-compartment open model
2.Two compartment
3. Multiple compartment
Mammillary model
Central compartment (comprises of plasma and highly perfused tissues such as lungs, liver,
kidneys) joined parallel to the peripheral compartment (comprises of less perfused organ) like
connection of satellites to a planet.
Catenary model
Compartments are joined to one another in a series like compartments of a train. This is
however not observable physiologically/anatomically as the various organs are directly linked to
the blood compartment.
Types One-compartment open model
One-compartment open model, i.v. bolus administration.
One-compartment open model, continuous i.v. infusion.
One-compartment open model, e.v. administration, zero-order absorption
One-compartment open model, e.v. administration, first-order
Physiological models
They are drawn on the basis of known anatomic and physiological data and thus present a more
realistic picture of drug disposition in various organs and tissues.
Two types
• Perfusion rate-limited models lipophilic drugs
• Diffusion-limited models hydrophilic drugs
ONE COMPARTMENT OPEN MODEL
Body is considered as a single, kinetically homogeneous unit that has no barriers to the
movement of drug
TWO-COMPARTMENT OPEN MODEL
Body tissues are broadly classified into 2 categories –
1. Central Compartment or Compartment 1
Comprising of blood and highly perfused tissues like liver, lungs, kidneys, etc. that
equilibrate with the drug rapidly.
Elimination usually occurs from this compartment.
2. Peripheral or Tissue Compartment or Compartment 2
Comprising of poorly perfused and slow equilibrating tissues such as muscles, skin, adipose,
etc. and considered as a hybrid of several functional physiologic units
ONE COMPARTMENT IV BOLUS ADMINISTRATION
Elimination rate constant= log C=logC0 - Ke t /2.303
Half-life = 0.693/Ke
Volume of distribution Vd= x/c
Volume of distribution Vd = IV bolus dose / C
Total body clearance = 0.693 Vd /t1/2
ONE-COMPARTMENT OPEN I.V. INFUSION
Steady state concentration, Css = Infusion rate / Clearance
Clearance = Ke * Vd
Steady state concentration, Css = Infusion rate/ Ke*Vd
Infusion rate R0 = Css * Clearance
Loading dose = Css *Vd
Loading dose = Infusion rate/ Ke
Loading dose =CP desired *Vd /F
PREVIOUS QUESTIONS
1. What does the word “open” mean in the one compartment open model?
a) The drug easily enters
b) The drug readily mixes with the blood
c) Unidirectional input and output
d) Easy absorption
Answer: c
2. How much time does an intravenously administered drug take to complete a complete circulation?
a) 5-8 min
b) 7-10 min
c) 1-3 min
d) 1 min
Answer: c
3. In the equation log C = log Co – KEt/2.303, what does Co stand for _______
a) Plasma drug concentration after 60 min of i.v. injection
b) Plasma drug concentration after 15 min of i.v. injection
c) Plasma drug concentration after 30 min of i.v. injection
d) Plasma drug concentration immediately after i.v. injection
Answer: d
4. What is meant by elimination half-life?
a) Time take for half of the amount of drug to get completely eliminated from only the organs
b) Time take for half of the amount of drug to get completely eliminated from only blood
c) Time take for half of the amount of drug to get completely eliminated from only plasma
d) Time take for half of the amount of drug to get completely eliminated from the body as well as plasma
Answer: d
5. What is the equation to find out the apparent volume of distribution?
a) Amount of drug in the body/plasma drug concentration
b) Plasma drug concentration/amount of drug in the body
c) 1 / plasma drug concentration
d) 1 / Amount of drug in the body
Answer: a
6. The i.v. bolus dosage is 500mg and the plasma drug concentration is 0.8 mg/ml.
What should be the volume of distribution?
a) 625 mg/ml
b) 625 l
c) 625 ml
d) 0.0016 mg/ml
Answer: c
Explanation: The apparent volume of distribution Vd is given by Amount of drug in the body (X) / plasma drug c
Thus 500/0.8=625.
7. Which organs comprise the central compartment in a two compartment model?
a) Muscles
b) Skin
c) Adipose
d) Liver
Answer: d
Explanation: The central compartment or the compartment 1 in a two compartment model comprises
of the blood and the highly perfused tissues like liver, lungs, and kidneys, etc. which equilibrate blood rapidly
. These compartments will have the elimination from them.
8. Which organ comprises the peripheral compartment in a two compartment model?
a) Liver
b) Lungs
c) Kidneys
d) Muscles
Answer: d
Explanation: The peripheral compartment or compartment 2 in a two compartment model comprises
of poorly perfused and slowly equilibrating tissues such as muscles, skin, adipose tissue, etc.
These are considered as a hybrid of several functional physiologic units.
9. About steady state concentration during IV administration
a. Directly proportional to Vd
b. Inversly proportional to Vd
c. Directly proportional to infusion rate
d. Inversly proportional to rate of elimination
e. Both B, C and D
Ans. E
Steady state concentration, Css = Infusion rate/ Ke*Vd
