Tuesday, 22 January 2013

Casodex Zytiga Combo

Casodex is a widely used antiandrogen and some oncologists are combining Casodex with Zytiga. This combination has promising potential by using an antiandrogen such as Casodex together with a hormone boisynthesis inhibitor Zytiga.

Zytiga blocks CYP17 and prevents all androgens including testosterone from being made. In the absence of testosterone caused by Zytiga the antiandrogen has a much better chance of working, since there is no testosterone to compete with its own binding to the androgen receptor (AR). So Casodex should bind better to the androgen receptor in the presence of Zytiga and so will inrease its activity as an antiandrogen.

There is also an added bonus of this combination as a result of drug meatbolism. Casodex inhibits the liver enzyme CYP3A4 which is the same enzyme that deactivates Zytiga to its inactive N-oxide metabolite. So Casodex will reduce the metabolism and clearance of Zytiga and increase its half life.

Co-administartion of Casodex with the drug Midazolam, which is a CYP3A4 substrate, showed that this increased the drug concentration 1.5 fold and doubled the half-life. This would be a useful effect when considered in context of the Casodex Zytiga combo. In practise this means that

a) The same dose of Zytiga (1000mg, i.e. 4 x 250 mg tablets) can be used for double the effect.

b) The dose of Zytiga could be reduced to 500mg (i.e. 2 x 250 mg tablets) with an equal effect.

The end result of combining Casodex with Zytiga is therefore to:

1) Increase Casodex antiandrogenic activity.

2) Increase Zytiga effects by 2-fold.

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