Definition
History
role of biotransformation
where drug biotransformation occur
the pathway of drug metabolism
phase 2 reaction
plasma level time curve of mephenytoin
factors affecting drug metabolism
importance of biotransformation
2. Biotransformation
The conversion of molecules from one form to another
within an organism, often associated with change
(increase, decrease, or little change) in pharmacologic
activity; refers especially to drugs and other xenobiotics.
The metabolism of a drug or toxin in a body is an
example of a biotransformation. The body typically
deals with a foreign compound by making it more water-
soluble, to increase the rate of its excretion through the
urine.
3. History
Welsh biochemist
Metabolism of sulfonamides,
benzene, aniline, acetanilide,
phenacetin, thalidomide and
stilbesterol
Metabolism of TNT (Trinitrotoluene)
with regard to toxicity in munitions
(1942)
1909 - 1979
Richard Tecwyn Williams
4. The role of biotransformation
Alteration or termination of drug activity
Converts pro-drug to active compound
Coverts less active drug to more active drug
Produces toxic compound
Terminates drug actions
6. The pathways of drug metabolism
phase І
phase II
Phase 1 reaction include oxidation ,reduction and
hydrolysis.
Phase 1 reactions usually convert the parent drug to a
more polar metabolite by introducing or unmasking a
functional group (-OH, NH2 , -SH). If phase 1
metabolites are sufficiently polar, they may be readily
excreted.
7.
8.
9. Phase 2 reactions:- An endogenous An
endogenous substrate such as glucuronic acid,
sulfuric substrate such as glucuronic acid,
sulfuric acid, acetic acid, or an amino acid
combines acid, acetic acid, or an amino acid
combines with the functional group to form a
highly with the functional group to form a
highly polar conjugate.
13. Factors affecting Drug Metabolism
Genetic factors
Diet & environmental factors
Age & sex
Drug-drug interactions during
metabolism
Interactions between drugs &
endogenous compounds
Disease affecting drug metabolism
14. drug metabolism plays a major role and determines the
fate of the prospective drugs.
Drug metabolism must take place only after the drugs
reach their specific target site and produce the desired
effects.
Drug metabolism has an important role in the
determination of the pharmacokinetic (PK) parameters
like- Oral Biioavailability
Clearane and Half life.
Drug metabolism is very essential in the toxicity studies
too.
The persistence of the compounds in the systemic
circulation for long period causes toxicity.
Importance of Biotransformation