Further, unlike Phase I, Phase II reactions almost invariably inactivate a given drug. The most important difference between Phase I and II reactions is that the former one is molecule-autonomous whereas the latter one creates a covalent bond with another molecule or its part. Type I and II would be therefore more appropriate. isoniazid) or separately (Phase I or Phase II). The usual classification of drug metabolism enzymes and reactions as Phase I or II is somewhat misleading, as these reactions affect some drugs in a reverse order (Phase II followed by Phase I, e.g. The principal effectors of drug metabolism are the cytochrome P450 (CYP450) enzymes. The contribution of these organs to drug metabolism is incompletely understood, but certainly much smaller. They are therefore expressed also at other interfaces of the body with the environment such as the skin, lungs, and the kidney. As drug metabolizing enzymes also metabolize certain endobiotics, induction and inhibition may result in metabolic disorders.ĭrug metabolizing enzymes have evolved primarily as a defense against non-medical chemicals taken up from the environment. The induction and inhibition of drug metabolism constitute examples of pharmacokinetic drug interactions. with rifampin or carbamazepine and, in the case of CYP2D6, in the presence of additional gene copies. It is higher in patients treated with transcriptional inducers of drug metabolizing enzymes, e.g. macrolids and conazols), and in those with liver disease or insufficient hepatic blood flow. It is lower immediately after birth, in carriers of inactivating mutations in drug metabolizing enzymes, in patients treated with drugs inhibiting these enzymes ( e.g. Hepato-intestinal drug metabolism is highly variable not only among patients but even in one particular individual over time.

Drugs completely inactivated during the first-pass through these organs must be given parenterally, similarly to poorly absorbed drugs. The principal organs of drug metabolism are the liver and (for orally taken drugs) the small intestine. The involved chemical modifications incidentally decrease or increase a drug’s pharmacological activity and/or half-life, the most extreme example being the metabolic activation of inactive prodrugs into active drugs, e.g. The primary objective of drug metabolism is to facilitate a drug’s excretion by increasing its water solubility (hydrophilicity).

Doctors in training cyp450 inducer