Beruflich Dokumente
Kultur Dokumente
Dr.U.P.Rathnakar MD.DIH.PGDHM
K.M.C. Mangalore.
Biotransformation:Metabolism
Chemical alteration of the drug in
a living organism is called bio-
transformation.
Lipid soluble →Water soluble
So that not reabsorbed in Kidney
Site-Mainly liver
Others-Kidney, lungs, plasma
Metabolism: Consequences
End result is usually inactivation of a drug- But
intermediate product need not be!
1. Active→Inactive
Eg. Phenytoin → p-Hydroxyphenytoin
2. Active→Active
Eg.Codeine → Morphine,
3. Active → Toxic. Eg. P.Mol →NABQI
4. Inactive → Active,
-Prodrug
Eg. Prednisone→ Prednisolone
L-Dopa →Dopamine
Metabolism:Phases: I & II
Catalyzed by enzymes
2. Reduction:
Opp.of Oxidation
Eg. Choramphenicol, Methadone
3. Hydrolysis:
Addition of water
Eg.Esters-Procaine, Succinylcholine,
Amides- Procainamide, Lignocaine
4. Others-Cyclization and decyclization
Tubular
Glomerular Tubular
reabsorption
Renal Filtration secretion
excretion
Glomerular Filtration
Mol.size
Depends on Renal blood
flow
Plasma protein binding
Tubular secretion-Active
Carrier mediated
Not affected by PPB
Penicillin, Probenecid, Quinine
May use same carrier-Non-
specific
Probenecid inhibits penicillin
secretion
Tubular Reabsorption-Passive
Depends on pH and ionization
Strongly acidic and alkaline-Unionized-
Excreted
Weakly acidic-Ionized in alkaline
medium-not absorbed. Eg. Alkaline urine
and aspirin toxicity
Weakly basic-Ionized in acidic urine
Eg. Acidification of urine –NH4cl or Vit-
C-in Amphetamine poisoning
Factors affecting renal excretion
Excretion-Other routes
Lungs: Alcohol, G.A,
Faeces: Drugs not absorbed and secreted with
bile
Bile:Excreted in Bile→Reabsorbed from small
intestine-This cycle is E.H.circulation
Eg.E.Mycin
Skin: As and Hg
Saliva: KI, phenytoin. Li
Milk:Milk acidic →Alkaline drugs ionized and
accumulate. Eg. Tetracycline →ADE in infant
Kinetics of Elimination
Fundamental PK Parameters:
1. Vol.of distribution
2. B.A
3. Clearance
THE CLEARANCE OF A DRUG IS THE
THEORETICAL VOLUME OF PLASMA FROM WHICH
THE DRUG IS COMPLETELY REMOVED IN UNIT
TIME
Rate of elimination
CL= …………………………
Plasma conc.( C)
Elimination: First and Zero Order Kinetics
175
98 99
96.5
150 93.5
87.5
100
100
75
50
Elimination First order
100 mg administered[100%]
1 t1/2 50mg 50%
2 t1/2 25mg 75%
3t1/2 12.5 mg 87.5%
4t1/2 6.25.mg 93.75%
Take 4-5 halflives for complete
elimination of a drug
Clinical Importance of Half Life
t½ helps to determine the
duration of action of the
drug.
To determine the frequency
of drug administration.
To determine the time taken
to achieve the steady state.
Factors Influencing Drug dosage
4-5 half lives for steady state
Short half life → repeated admn.
Long half life→Takes long time to
reach steady state
So loading dose is given for
immediate effect
Maintainance dose is given to
maintain steady state
Therapeutic drug monitoring-TDM
Monitoring drug therapy by measuring plasma
conc.of drugs.
Indications
1. Drugs with low margin of safety-
Digoxin,Lithium
2. To check Pt. compliance.
3. If individual variations are large.- TCA.
4. Potentially toxic drugs used in presence of
renal failure-AMINOGYCOSIDES
5. When Pt. does not respond without reason
Fixed Dose Combinations[FDC]
Advantages Disadvantages
Better Pt.compliance Inflexible dose ratio
Synergistic effect Incompatible PK
Estrogen+Progesterone Increased toxicity-with
wrong combinations
Reduced side effect
Ignorance of contents
Aspirin+P.mol
Prevents microbial
resistance
INH+Rifampin+PZI
Improved efficacy Eg?
Levodopa+Carbidopa
How to prolong duration of action
of a drug?
Prolong absorption from site of administration
Oral- SR tablets, CR. ?Eg
Parenteral: Less soluble form, oily prep, adrenaline
TTS ?Eg
Increase PPB ?Eg
Slow down Metabolism ?Eg
Reduce Renal Excretion ?Eg