Tacrolimus Cytochrome P450 isoenzyme inducers

In vitro studies with rat and human liver microsomes have found that tacrolimus is extensively metabolised by the cytochrome P450 isoenzyme CYP3A4. This means that drugs that induce CYP3A4 may potentially reduce the serum levels of tacrolimus. 

Tacrolimus is extensively metabolised by the cytochrome P450 isoenzyme CYP3A4, and phenytoin is a known inducer of this system. Phenytoin is therefore predicted to decrease tacrolimus levels. In the first case, it was suggested that tacrolimus might have inhibited the metabolism of phenytoin, although other factors may have had some part to play in the raised phenytoin levels. ... 

This interaction is thought to occur because rifampicin, a known enzyme inducer, increases the metabolism of the tacrolimus by the cytochrome P450 isoenzyme CYP3A4 in the liver and small bowel, and by inducing P-glycoprotein, so that the tacrolimus is cleared more rapidly. 

St John s wort induces the cytochrome P450 isoenzyme CYP3A4 and affects the transporter protein P-glycoprotein. CYP3A4 and P-glycoprotein are involved in the metabolism and clearance of tacrolimus, so an increase in their effects would be expected to result in a decrease in tacrolimus levels. - ... 

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