Zytiga is metabolised by the liver enzyme CYP3A4 to an inactive metabolite that is excreted from the body. The usual half life of Zytiga is 12 hours and this rate of drug clearance is goverened by the activity of the CYP3A4 enzyme. Modulators of this enzyme will therefore affect the rate of clearance and hence activity of Zytiga.
There are 2 types of modulators of CYP3A4, inducers and inhibitors.
1. CYP3A4 inducers e.g. Rifampicin, Xtandi (Enzalutamide)
A CYP3A4 inducer will elevate the levels of this enzyme in the liver and increase the metabolism of Zytiga resulting in a shorter half life and reduced drug activity.
A clinical trial is underway to investigate the effect of Rifampicin which is a potent inducer of CYP3A4 on the metabolism of Zytiga (Abiraterone). This will look at the effect of Rifampicin exposure on the effects of a single 1000 mg dose of Zytiga and measure the levels in the plasma and rate of clearance to calculate the half life. The results of this study will have implications on the combined use of Xtandi with Zytiga since Xtandi (Enzalutamide) is also a potent inducer of CYP3A4 and may result in lower activity of Zytiga.
2. CYP3A4 inhibitors e.g. Ketoconazole, Itraconazole.
On the other hand a CYP3A4 inhibitor will block the activity of this enzyme and reduce the metabolism of Zytiga resulting in a longer half life and increased activity due to prolonged drug exposure.
Another clinical trial is investigating the effect of Ketoconazole on the metabolism of Zytiga. In theory since Ketoconazole is an inhibitor of CYP3A4 it should decrease the rate of Zytiga metabolism and prolong its duration of action. This study is investigating the effect of Ketoconazole exposure to a single 1000 mg dose of Zytiga to measure its half life. This could mean that Ketoconazole may be succesfully combined with Zytiga to increase its activity and would mean that lower doses of both drugs could be used together.
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