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PLASMA HALF LIFE
(t1/2)
 Minimum
Effective
Concentration
(MEC): The plasma drug concentration
below which a patient’s response is too small
for clinical benefit.
 Peak
Plasma & Trough Concentration :
The maximum & minimum drug conc.
achieved during repeated dosing cycles.
 Target Concentration : The plasma
concentration required to produce desired
therapeutic effect.
Definition:
The time required for the concentration of the
drug in the plasma to decrease to one half of
its initial value after the peak has been
reached.
 It is designated as t ½.
 A useful parameter derived from Vd & CL.
 Important for rational drug therapy because it
helps in designing & planning the dosage
regimens


Assimilation kinetics
Elimination kinetics
 Plasma half life is a measure of the
elimination kinetics
 Peak level- beyond which further assimilation
cannot take place and elimination processes
take over
 It can be calculated by following relationship:
t ½ = 0.7 x Vd
CL
Plasma Concentration
a
10000
Distribution and Elimination
C0
1000
b Elimination only
100
10
Distribution equilibrium
1
0
1
2
3
4
Time
5
6

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Decline in Plasma Concentration starting at
any steady-state plasma concentration (100
%) of a drug , it will fall as follows:
After 1 t ½ to 50 %
After 2 t ½ to 25 %
After 3 t ½ to 12.5 %
After 4 t ½ to 6.25 %
After 5 t ½ to 3.125 %
t½
Plasma conc. (mg)
0
100
1
50
2
25
3
12.5
4
6.25
5
3.125
1.
2.
3.
4.
5.
6.
7.
8.
9.
Volume of distribution
Plasma protein binding
Clearance
Kinetics Pattern
Presence of second drug
Diseases
Active metabolites
Enterohepatic circulation
Hepatic blood flow

Large Vd = long t1/2
 Albumin
 Globulin
 Free drug
 Bound drug
 Class I drugs
 Class II drugs

Increased clearance = decreased t1/2
 First order kinetics/Exponential kinetics/linear
 Uniform or fixed fraction of drug is eliminated in a unit
time
 t1/2 independent of the drug concentration
 constant t ½
 Zero order kinetics/Saturation kinetics/non-linear
 Michaelis Menten kinetics
 Fixed amount of drug is eliminated in a unit of time
 Increase dose = t ½ prolonged
First order
 Plasma conc. is 100mg and fraction eliminated is
10%/hr
 So after 1 hr 10% is eliminated =10mg, leaving
90mg
 After 2nd
hr again 10% is eliminated =9mg, leaving
81mg
 After 3rd hr 10% of 81mg is eliminated =8.1mg,
leaving 72.9mg
 After 4th hr 10% of 72.9mg= 7.29mg, leaving
65.6mg
Changing the dose t1/2 is not changed
Time (hrs)
0
1
2
3
4
5
6
Plasma conc
(mg)
100
90
81
72.9
65.6
59.04
53.14
Plasma conc
(mg)
200
180
162
145.8
131.22
118.01
106.29
Zero order
 100mg dose and amount eliminated is 10mg/hr
 So after 1hr 90mg remains
 After 2hrs 8omg remains
 After 3hrs = 70mg
 4hrs =60mg
 5hrs = 50mg
Increasing dose will increase t1/2 as enzymes
become saturated and elimination capacity
decreases
Time (hrs)
0
1
2
3
4
5
10
Plasma conc
(mg)
100
90
80
70
60
50
-
Plasma conc
(mg)
200
190
180
170
160
150
100
Drugs following zero order kinetics
 Aspirin
 Phenytoin
 Alcohol
Enzyme inducers ----- ↑ metabolism (↓ t½ )
Enzyme inhibitors ----- ↓ metabolism (↑t½)
 Diseases of organ of metabolism/excretion
 Hepatic & renal disease

Change in Vd

Change in plasma protein binding

Biological half life (duration of action) longer
than plasma half life
?

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Aspirin
Omeprazole

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Aspirin – salicylate
Morphine – morphine 6 glucoronide

Drugs excreted in bile are reabsorbed from
intestine and plasma half life is prolonged

Rifampin
Morphine



Decreased hepatic blood flow e.g. in
cardiogenic
shock,
cardiac
failure,
hemorrhage
Prolonged t ½ of drugs with flow dependent
CL/extensive hepatic first pass metabolism

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Rate of elimination
Duration of action
Dosing interval
Designing a dosing regimen
Time for steady state concentration
Time for complete elimination

t ½ indicates rate of elimination
97 % drug eliminated in 5 t ½
Increase t1/2 – elimination is slow
Decrease t1/2 – elimination is fast

t ½ indicates the duration of action of a drug
longer t ½ -long duration of action
shorter t ½ -short duration of action

t ½ indicates the dosing interval
longer t ½ -long dose interval
shorter t ½ -short dose interval
t ½ is important for designing a dosage regimen.
It is a plan for drug administration over a period of
time.
 The interval between doses should not be less than
4 t ½.
 Drugs with short half life --- More frequent dosing.
 Drugs with long half life --- Less frequent dosing.
 Loading dose for drugs with large Vd .



Time for Steady State (SS)
 Rate of elimination equals the Rate of drug
administration
 Time to reach SS is 4-5 t ½
 Time to reach SS is not affected by dose of drug

Time for complete elimination
 Important incase of certain adverse effects
When constant dose of a drug is repeated before 5
t1/2. it would achieve higher peak concentration,
because some remnant of the previous dose will be
present in the body
 This continues with every dose until progressively
increasing rate of elimination balances the amount
administered over the dose interval
 Plasma concentration plateaus and fluctuates about
an average steady state level

Plasma Half Life of Some drugs:

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Esmolol 09 Min
Aspirin 15 Min
Morphine 1.9 Hours
Propranolol 3.9 Hours
Digoxin 50 Hours
Digitoxin 161 Hours
Thank you!