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PharmD clinical pharmacy program Level 3, Semester 2 Biopharmaceutics & Pharmacokinetics (PT608(

Pathways of Drug Metabolism

Phase I reactions: (reactions that alter the basic chemical structure of the

parent molecule).

Phase II reactions: (reactions that result in the attachment of some

endogenous substance to the parent molecule – or conjugation reactions).

Phase I reactions

Phase 1 reactions often occur in the cytosol, mitochondria, and microsomes (a

subcellular component containing membrane-associated enzymes on the smooth

endoplasmic reticulum) of the liver and other organs.

1- Oxidation

- Oxidation (e.g., the addition of oxygen or the removal of hydrogen from the parent

molecule) is a common Phase 1-type reaction.

Microsomal oxidation is a common mechanism of metabolism of many drugs and

nutrients.

- Cytochrome P-450 reductase and the many isozymes of cytochrome P-450 (CYP)

are capable of catalyzing oxidation reactions.

- Examples of microsomal oxidation reactions are

 C-oxidation or C-hydroxylation of aliphatic or aromatic groups;
 N-or O-dealkylation;
 N-oxidation or N-hydroxylation;

 Sulfoxide formation;
 Deamination; and
 Desulfuration.

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