Scribd
Upload
121 views20 pages

Half Life of Drugs

The document discusses the half-life of drugs, which is the time required for a drug's concentration in the body to reduce by half. It notes there are alpha and beta half-lives, where the alpha half-life refers to distribution and the beta half-life to elimination. Factors like plasma protein binding, volume of distribution, renal or hepatic function, active metabolites, and enzyme induction or inhibition can impact a drug's half-life. Shorter half-lives require more frequent dosing while longer half-lives allow less frequent dosing to maintain therapeutic drug levels. The clinical significance of half-life includes effects on drug elimination rate, duration of action, dosage intervals, time to steady state levels, and complete elimination

Uploaded by

Aqsa Rehman
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
121 views20 pages

Half Life of Drugs

The document discusses the half-life of drugs, which is the time required for a drug's concentration in the body to reduce by half. It notes there are alpha and beta half-lives, where the alpha half-life refers to distribution and the beta half-life to elimination. Factors like plasma protein binding, volume of distribution, renal or hepatic function, active metabolites, and enzyme induction or inhibition can impact a drug's half-life. Shorter half-lives require more frequent dosing while longer half-lives allow less frequent dosing to maintain therapeutic drug levels. The clinical significance of half-life includes effects on drug elimination rate, duration of action, dosage intervals, time to steady state levels, and complete elimination

Uploaded by

Aqsa Rehman
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
You are on page 1/ 20

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 ■ ZERO ORDER KINETICS


 AKA exponential kinetics  AKA non linear kinetics
 Fixed fraction is eliminated in  Fixed amount of drug is
unit time eliminated
 T ½ not affected by dose of
 T ½ affected by dose of drug
drug
 Rate of Elimination proportional  Elimination not proportional
to plasma concentration to plasma concentration
 Elimination processes are not  Elimination process is
saturated saturated
 Drugs in Therapeutic doses  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

You might also like