Drug biotransformation enzyme systems, cytochromes P450

For most drugs, oxidative biotransformation is performed primarily by the mixed-function oxidase enzyme system, which is present predominantly in the smooth endoplasmic reticulum of the liver. This system comprises (1) the enzyme NADPH cytochrome P450 reductase (2) cytochrome P450, a family of heme-containing proteins that catalyze a variety of oxidative and reductive reactions and (3) a phospholipid bilayer that facilitates interaction between the two proteins. Important exceptions to this rule are ethyl alcohol and caffeine, which are oxidatively metabolized by enzymes primarily present in the soluble, cytosolic fraction of the liver. 

Cytochrome P450 electron transport systems are an important feature of biotransformation in animal bodies. Biotransformation is a series of enzyme-catalyzed processes in which potentially toxic and usually hydrophobic substances are converted into less toxic water-soluble derivatives that can then be more easily excreted. Substrates for biotransformation include endogenous substances, such as cholesterol, and foreign molecules, called xenobiotics, such as drugs and nonnutritive components of food (e.g., glycosides and numerous fatty acid and amino acid derivatives). 

Formal PK drug-drug interaction studies have not been performed with Prialt. As ziconotide is a peptide, it is expected to be completely degraded by endopeptidases and exopeptidases (Phase I hydrolytic enzymes) widely located throughout the body, and not by other Phase I biotransformation processes (including the cytochrome P450 system) or by Phase... 

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