Phenytoin is extensively metabolised by hydroxylation, principally by CYP2C9, although CYP2C19 also plays a role. These isoenzymes show genetic polymorphism, and CYP2C19 may assume a greater role in individuals who have a poor metaboliser phenotype of CYP2C9. The concurrent use of inhibitors of CYP2C9, and sometimes also CYP2C19, can lead to phenytoin toxicity. In addition, phenytoin metabolism is saturable (it shows nonlinear pharmacokinetics), therefore, small changes in metab- olism or phenytoin dose can result in marked changes in plasma levels. Fosphenytoin is a prodrug of phenytoin, which is rapidly and completely hydrolysed to phenytoin in the body. It is predicted to interact with other drugs in the same way as phenytoin. No drugs are known to interfere with the conversion of fosphenytoin to phenytoin.
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