Question

12 Pharmacokinetics Model Analysis. An impulsive dose of one unit strength of drug X is given to a subject intravenously, and its disappearance from blood is biexponential. The drug in blood exchanges reversibly with drug in tissues and is catabolized in tissues. It is not eliminated in or from the body in any other manner. A dose 01% unit h produces a blood response curve of half the magnitude of a one unit strength times the E4. dose, and a dose of two unit strength produces a blood response curve 1.5 magnitude of a one unit strength dose a) Draw a diagram of a compartmental model of the disposition of this drug in blood and tissues and state a major assumption or restriction on its applicability. b) How many modes are there in the response measured in the blood? c) Is it possible to obtain the rate of catabolism of this drug from blood-borne measurements of the drug concentration? Explain your answer and, again, state any assumptions or restrictions concerning such results. d) Describe how you would estimate the total body equivalent distribution volume Wo of the drug from the same intravenous impulse response experiment described above. (Remember that VD is a steady state concept, so you might want to consider a steady state "thought experiment" with a constant input to derive some useful relationships.) There is more than one way to solve this problem. OnnFs for the five-compartment

Answer 1

In pharmaco dynamics and pharmacoanalysis compartment model is an important concept.In the pharmacology compartment means the entire body,and all of the organs and tissues are considered as a compartment or a gaint bucket.We are considering the body as a central compartment (compartment 1).We are administering the drug that is some where outside the compartment that means outside the body to the central compartment or compartment 1

from the central compartment drug leaves from the compatment 1 by two ways,ie ,through :

• compartment 2 or to the peripheral compartment and
• drug leaves the body

compartment 2 means,peripheral compartment where the drug exchange and absorption occurs and can return to the central compartment and leaves the body and it doesnot re-enter the body.

a)

• It helps to know the drug absorption,distribution and elimination
• it is very simple and convenient to know the drug concentration
• 

The major assumption of this model is the clearance occurs from the central compartment (blood compartment)

b)

where AUC is area under plasma concentration and C represents the time interval

Vd = dose/plasma concentration

where V_d is the apparent volume of drug disperses in order to produce the observed plasma concentration

c)

catabolism in the sense break down of complex molecules in to simpler one,It is a process occuring in the drug metabolism.

first we have to know the half life t _1/2 is the time required to reduce the drug concentration by half.To know the half life t_1/2 = 0.693 X Vd /CL,

where CL is the clearance ,

After agiving a drug its concentration is fall according to the elimination rate constant.

Thus we know the catabolism of drug

d)Vd is the volumeof drug distribution

it can be calculated by the Total dose of the drug/concentration 100mg/dl

if the dose is 500ml

Vd = 500mg/concentration 100 mg/dl and is expressed in L (litre)

CL=F x dose/AUC, where F is the fraction of drug absorbed