N,O-diacetyl-p-aminophenol. Example 2: At 37
C and pH 2.5, norethindrone
reacts with isoniazid form hydrazone XXI, in 6 min.
Examples Drugs which undergo non-enzymatic elimination:
• Mustin HCl converted into Ethyleneimonium
• Atracurium converted into Laudanosine and Quaternary acid
• Hexamine converted into Formaldehyde
• Clorazepate converted into Desmethyldiazepam
16.6 Factors Affecting Biotransformation
The process of transformation in vitro can be affected by numerous factors (Renton
1986) such as:
1. Physiochemical properties of the drug
2. Chemical properties of the drug
3. Biological factors
16.6.1 Physiochemical Properties of Drug
It includes the molecular size, acidity/basicity, pKa values, lipophilicity, interaction
with drug metabolizing enzymes.
16.6.2 Chemical Properties of Drug
16.6.2.1 Enzyme Induction
Certain enzymes get induced or activated when they are exposed to a specific drug.
These agents are called enzyme inducers. These can be several drugs and pesticides,
or even cigarette smoke.
16.6.2.2 Enzyme Inhibition
Inhibition of enzyme activity due to exposure to a specific drug is a property which
affects the biotransformation process. The inhibition can be due to a direct or indirect
mechanism. Direct inhibition is further achieved by three mechanisms—competitive
inhibition, non-competitive inhibition, product inhibition. Example: allopurinol
inhibits xanthine oxidase; whereas indirect inhibition is achieved by two
mechanisms, i.e. repression and altered physiology. Examples: actinomycin,
puromycin.
16 Biotransformation: Basics and Applied Perspectives
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