HALF LIFE OF DRUGS

DEFINITION:

■ Time required for the concentration of drug to fall to half of its

initial concentration , after reaching its peak.
■ ALPHA HALF-LIFE
 Plasma or distribution half life
 rapid decrease in plasma levels is due to drug distribution from
circulation

■ BETA HALF-LIFE
 Elimination half life
 a slower decrease in plasma drug levels due to drug metabolism and
excretion from the body.

■ THIOPENTONE SODIUM
 DOA – 5 to 10 min
 Elimination half life – 7 to 10 hours
 Alpha half life – 2 to 5 minutes
FACTORS AFFECTING HALF-LIFE:

Plasma protein binding

Volume of distribution

Pharmacokinetic pattern

Renal / Hepatic diseases

Active metabolites

Enterohepatic circulation
Enzyme induction /
Inhibition
1. PLASMA PROTEIN BINDING

 Having plasma protein binding – longer half life

 Plasma protein binding ∝ Half-life
 Acidic drugs – albumin
 Basic drugs – globulin
 Protein bound drug – no pharmacological activity
can not be eliminated
can not be
metabolized
 Example: Warfarin – 40 hours
2. VOLUME OF DISTRIBUTION

 ↑ volume of distribution - ↑ half life

 t½ = 0.693 × Vd /CL

3. RENAL / HEPATIC DISEASES

 T ½ Increased in renal disease – less excretion
 T ½ Increased in hepatic diseases – no metabolism
 EXAMPLE: Aminoglycosides
 Normally excreted through glomerular filtration
 4. PHARMACOKINETIC PATTERN
■ FIRST ORDER KINETICS
 AKA exponential kinetics
 Fixed fraction is eliminated in
unit time
 T ½ not affected by dose of
drug
 Rate of Elimination proportional
to plasma concentration
 Elimination processes are not
saturated
 Drugs in Therapeutic doses
■ ZERO ORDER KINETICS
 AKA non linear kinetics
 Fixed amount of drug is
eliminated
 T ½ affected by dose of drug
 Elimination not proportional
to plasma concentration
 Elimination process is
saturated
 Drugs in toxic doses
FIRST ORDER ZERO ORDER
KINETICS KINETICS
SIGNIFICANCE:

■ ↑ dose - ↑ plasma concentration - ↑ T ½

■ Toxic doses – zero order kinetics
■ Certain drugs follow zero order kinetics in therapeutics, after a small
increase in dose
1. Alcohol
2. Phenytoin
3. Salicylates
■ Alcohol stays in blood because of zero order kinetics
5. ACTIVE METABOLITES
 Convert to active metabolites – Longer half life
 EXAMPLE:
 Diazepam → desmethyldiazepam ( half-life 72 hours)

6. ENZYME INDUCTION / INHIBITION

■ Enzyme induction – metabolizing enzymes are activated – half
life decreased
■ Enzyme inhibition – metabolizing enzymes are inhibited – half
life increased
7. ENTEROHEPATIC CIRCULATION

■ Some Drugs Metabolized in liver

■ Conjugated with glucuronic acid
■ Excreted into bile
■ In intestine – conjugate broken down by bacteria
and enzymes
■ Active drug – released and reabsorbed
■ Drugs have longer T ½
■ Example : Rifampicin, digitoxin
CLINICAL SIGNIFICANCE OF HALF-LIFE
■ Rate of elimination
■ Duration of action
■ Dosage intervals
■ Time for steady state
■ Time for complete elimination
1. RATE OF ELIMINATION

■ Shorter half life – administered in frequent doses

■ Longer half life – administered less frequently
■ About 90-95% of drug is eliminated after four half lives

2. DURATION OF ACTION

■ DOA directly proportional to T ½

3. INTERVAL BETWEEN DOSES

 Short half life – short intervals to maintain effective plasma

levels – more doses
 Long half life – long intervals – less doses

4. TIME FOR COMPLETE ELIMINATION

 Short half life – short time for complete elimination

 90-95% drug – eliminated after 4 to 5 half lives
 5. TIME FOR STEADY STATE
 Basically steady state is
Rate of Administration= Rate of Elimination
I/V
Administratio
n
SIGNIFICANCE OF STEADY STATE

■ Effective pharmacological management of diseases.

■ Antibiotics and Drugs given for long term use – antihypertensives
require steady state concentration to be maintained for better
effect
■ Serum concentrations of antibiotics need to remain within a
clinically effective range for optimal treatment.
■ Concentrations below this range could fail to treat infections
■ levels above this range could cause toxicity. 
■ Subtherapeutic concentrations correlate with antibiotic resistance
■ therapeutic drug monitoring should take place in a steady state.
SITUATIONS INVOLVING INCREASED HALF-LIFE

■ Decreased renal plasma flow e.g. heart failure, shock

■ Increased volume of distribution
■ Decreased metabolism e.g. cirrhosis of liver
SITUATIONS INVOLVING DECREASED HALF-
LIFE
■ Decreased plasma protein binding
■ Increased metabolism
EXAMPLES
■ DRUGS HAVING HALF-LIFE
 Less than 2 hours
Aspirin (15 min) , Esmolol (9 min) , Dobutamine (1min)
 Between 2-5 hours
Acetaminophen (2-3 hours) , Atropine (2 hours)
 Between 10-24 hours
Practolol (13 hours)
 Greater than 36 hours
Digoxin (39 hours) , Diazepam (72 hours)
THANK YOU