DRUG METABOLISM
The process of drug metabolism is characterized by alterations of a drug’s chemical structure through
various reactions in order to yield a drug metabolite which usually has a lower potency than the parent
compound. Drug metabolism is encapsulated by reactions that involve the enzymes systems which have
been developed through life as a defence mechanism against foreign substances and toxins. There is a
general trend and process where an oily drug that is insoluble in water becomes converted to a drug that
is polar. This process is achieved through modification of biological activity or change in lipid solubility
so that excretion can be achieved with relative ease.
The conversion includes three types or forms of transformations.
• Pharmacological inactive to active form.
• Active to another form of active drug.
• Active to inactive.
Most enzymes systems that are most frequently employed for these opportunities can be categorized
into two as follows.
Phase 1: These enzymes are either oxidative or reductive.
Phase II: These on the other hand are conjugative.
Classification drugs biotransformation phase.
1.Phase 1 reaction
• Oxidative
• Reductive
• Hydrolytic
2.phase 2 reaction
• Conjugation reaction
phase 1 reaction.
Phase 1 reactions are catabolic and the products are often more chemical reactive and hence
paradoxically, sometimes more or carcinogenic than the parent drug. Phase 1 enzymes act by causing
the drug molecule to undergo oxidation or more rarely reduction.
The cytochrome P450 enzyme superfamily is the primary phase 1system involved in the oxidative
metabolism of drugs and the other chemicals. Phase 1 reaction often introduce a reactive group such as
hydroxylase group then serves as the point of attack for the complementary system to attach a
substituent such as glucuronic acid. Many hepatic drug metabolism enzymes, including CYP enzymes
are embedded in smooth endoplasmic reticulum. Enzyme inhibition is the most frequently observed
result of CYP modulation and is the primary mechanism for drug-drug pharm kinetics interactions.
Competitive inhibition, where in two drugs are vying for the same active site and two drugs with the
highest affinity for the site wins out. Addition of second drug with the greater affinity for the enzyme
inhibits metabolism of the primary drug, and elevated primary drug blood or tissue concentration is the
result. Each drug has its own unique degree of affinity for the CYP enzyme active site, and the degree
of inhibition depends on how avidly the secondary drugs binds to the enzyme active site. Enzyme
induction of the drug of drug metabolizing activity can be due to either synthesis of new enzyme protein
or to decrease in the proteolytic degradation of enzyme.
The process of drug metabolism is characterized by alterations of a drug’s chemical structure through
various reactions in order to yield a drug metabolite which usually has a lower potency than the parent
compound. Drug metabolism is encapsulated by reactions that involve the enzymes systems which have
been developed through life as a defence mechanism against foreign substances and toxins. There is a
general trend and process where an oily drug that is insoluble in water becomes converted to a drug that
is polar. This process is achieved through modification of biological activity or change in lipid solubility
so that excretion can be achieved with relative ease.
The conversion includes three types or forms of transformations.
• Pharmacological inactive to active form.
• Active to another form of active drug.
• Active to inactive.
Most enzymes systems that are most frequently employed for these opportunities can be categorized
into two as follows.
Phase 1: These enzymes are either oxidative or reductive.
Phase II: These on the other hand are conjugative.
Classification drugs biotransformation phase.
1.Phase 1 reaction
• Oxidative
• Reductive
• Hydrolytic
2.phase 2 reaction
• Conjugation reaction
phase 1 reaction.
Phase 1 reactions are catabolic and the products are often more chemical reactive and hence
paradoxically, sometimes more or carcinogenic than the parent drug. Phase 1 enzymes act by causing
the drug molecule to undergo oxidation or more rarely reduction.
The cytochrome P450 enzyme superfamily is the primary phase 1system involved in the oxidative
metabolism of drugs and the other chemicals. Phase 1 reaction often introduce a reactive group such as
hydroxylase group then serves as the point of attack for the complementary system to attach a
substituent such as glucuronic acid. Many hepatic drug metabolism enzymes, including CYP enzymes
are embedded in smooth endoplasmic reticulum. Enzyme inhibition is the most frequently observed
result of CYP modulation and is the primary mechanism for drug-drug pharm kinetics interactions.
Competitive inhibition, where in two drugs are vying for the same active site and two drugs with the
highest affinity for the site wins out. Addition of second drug with the greater affinity for the enzyme
inhibits metabolism of the primary drug, and elevated primary drug blood or tissue concentration is the
result. Each drug has its own unique degree of affinity for the CYP enzyme active site, and the degree
of inhibition depends on how avidly the secondary drugs binds to the enzyme active site. Enzyme
induction of the drug of drug metabolizing activity can be due to either synthesis of new enzyme protein
or to decrease in the proteolytic degradation of enzyme.
