02.03.2.2 Inhibition

Conversely, the plasma levels of drugs may be increased when there is inhibition of enzymes. Thus, inhibition of enzymes will lead to a decreased rate of metabolism, and increased plasma concentration of drugs. Under these circumstances, a therapeutic drug may become a toxic drug. It was recently discovered that components of grapefruit juice are potent inhibitors of CYP3A4, and this can lead to dangerously high levels of the many drugs that are normally metabolised by this enzyme. Consequently, it is advisable not to take drugs at breakfast with a grapefruit or grapefruit juice, as this may lead to drug toxicity.

Ketoconazole, a commonly used anti-fungal agent is a potent inhibitor of CYP3A4. Thus, ketoconazole will increase the plasma concentrations of the drugs metabolised by this CYP, which includes the anti-HIV viral protease inhibitors. The anti-HIV viral protease inhibitors have the potential to be quite toxic, especially if their levels are raised.