Download Amount of drug at any time = drug conc * AVd Dose at any time= Css

LAB-3
PRACTICAL PHARMACOLOGY
2010-2011
Clinical parameters in
drug pharmacokinetics:
-
pharmacokinetics:
The processes to which the
drug undergone during its
movement through the
body. ( i.e. how the body
handles the drug)
Absorption:
1-Bioavailability
Bioavailability is the fraction
of administered drug that
reaches the systemic
circulation in a chemically
unchanged form
Clinical importance
Important to decide which
rout is suitable to
administer a given drug
Area under the curve(for IV)
(Auc(IV)):AUC (iv)= C0 / Ke
C0= concentration at zero time
Ke=elimination rate constant

2-The half-life
is the time required for the drug
concentration to change by fifty
percent. the t1/2 of a drug depends
upon 2 important factors:a-Apparent volume of
distribution(AVd).
b-Clearance of drug(CL).
percent
Clinical importance
important to be Known for drugs in which
drug conc. Is closely related to the
pharmacological effects e.g: phenytoin.
So used to predict the maximal effects both
on initiation and on termination of
therapy.
*It is of less value in drugs of which the
effects are poorly related to plasma conc.
e.g: diazepam
t1/2= (o.693*avd)/ cl
-AVd is apparent volume of
distribution
of a drug
-CL the drug clearance from the
body.( see interactive pharm.)

3-Volume of Distribution
The volume of distribution is a
hypothetical volume of fluid into
which a drug is dispersed. Although
the volume of distribution has no
physiologic or physical basis, it is
sometimes useful to compare the
distribution of a drug with the
volumes of the water compartments
in the body.
-The apparent volume of
distribution assumes that the
drug distributes uniformly, in a single
compartment. However, most drugs
distribute unevenly, in several
compartments, and the volume of
distribution does not describe a real,
physical volume, but rather, reflects
the ratio of drug in the extraplasmic
spaces relative to the plasma space.
Avd= amount of drug (dose)/ Co
Co = Auc*Ke
4-Elimination rate constant
(Ke):
is the amount of drug lost per unit
time.
Ke= o.693/t1/2
T1/2=o693/Ke


Clinical application
(t1/2) and is related to ke by the equation
t1/2 = 0.693/Ke
. The two parameters, together with
the initial concentration co, describe a
first-order (exponential) rate process.
The constancy of the process permits
calculation of the plasma volume
that would be cleared of drug,
5-Clearance(cl):-
The total body (systemic)
clearance, CLtotal or CLt, is the
sum of the clearances from the
various drug-metabolizing and
drug eliminating organs.
The kidney is often the major organ of
excretion; however, the liver also
contributes to drug loss through
metabolism and/or excretion into the bile.
A patient in renal failure may sometimes
benefit from a drug that is excreted by
this pathway, into the intestine and feces,
rather than through the kidney. Some
drugs may also be reabsorbed through the
enterohepatic circulation, thus prolonging
their half-life.(see interactive pharma.)
CL total= CL hepatic + CL renal+ CL
pulmonary+CL others.
It is not possible to measure and sum
these individual clearances. However, total clearance can be derived
from the steadystate equation:
CL total= rate of elimination/ Css
Css is conc.at steady state.
6-Steady state
Steady-state drug levels in blood:
Following the initiation of an IV
infusion, the plasma concentration of
drug rises until the rate of drug
eliminated from the body precisely
balances the input rate. Thus, a
steady-state is achieved in which the
plasma concentration of drug remains
constant.
*it means that dosing rate=
eliminating rate
(DR=ER).
* 5 t1/2 needed to achieve Css and
5 t1/2 to eliminate drug from
steady state.(see interactive pharma).
7-Amount of drug present in
body at any time(at certain
conc.):-
Amount of drug at any time
= drug conc * AVd
Dose at any time= Css * AVd.
summery
1-T1/2= 0.693*avd/ cl
T1/2=0.693/Ke
2-bioavailability=AUC(oral)/AUC(IV)
3-AUC= Co/Ke
4-Ke=o.693/t1/2
5-avd=dose/Co
6-Cltotal=avd*Ke
7- amount of drug at any time=drug conc*avd
Or Css*avd