CYP3A4, effect hepatic

St. John s wort, which has become very popular for the treatment of depression, has been shown to induce intestinal P-gp and intestinal and hepatic CYP3A4 in humans [140]. That mechanism explains the significant reduction in cyclosporin and anti-aids (e.g., indinavir) plasma concentrations. It is likely that similar effects will be noted with the compounds listed in Table 8 (although the effects noted in Table 8 are in the opposite direction of those seen in the presence of St. John s wort). 

Nevirapine induces hepatic CYP3A4 and 2B6. Coadministration of nevirapine and drugs primarily metabolized by CYP3A4 or CYP2B6 may result in decreased plasma concentrations of these drugs and attenuate their therapeutic effects. 

Following absorption across the gut wall, the portal blood delivers the drug to the liver prior to entry into the systemic circulation. A drug can be metabolized in the gut wall (eg, by the CYP3A4 enzyme system) or even in the portal blood, but most commonly it is the liver that is responsible for metabolism before the drug reaches the systemic circulation. In addition, the liver can excrete the drug into the bile. Any of these sites can contribute to this reduction in bioavailability, and the overall process is known as first-pass elimination. The effect of first-pass hepatic elimination on bioavailability is expressed as the extraction ratio (ER) ... 

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