The cytochrome P450 system is responsible for phase I oxidative metabolism of drugs. Following phase I metabolism, phase II metabolism makes the products of phase I metabolism more hydrophilic so that they can be more easily excreted. Due to this lesser role, phase II metabolism is generally less important in drug interactions (Sandson et al, 2005).
The most important family of enzymes for phase II metabolism is the uridine 5″-diphosphate
glucuronosyltransferases (UGTs). UGTs metabolize about 15% of FDA-approved medications (Dang et al., 2016). The metabolism of some psychotropic medications like lamotrigine and olanzapine occurs primarily through the UGTs.
The UGT system has some similarities to the CYP450 system. They:
1. Are also referred to be a number-letter-number notation.
2. Have various substrates, inhibitors, and inducers.
Medications metabolized by UGTs
Desvenlafaxine is metabolized by UGT1A1.
Lamotrigine is mainly metabolized by UGT1A4.
Olanzapine is mainly metabolized by CYP450 1A2 and UGT 1A4.
GeneSight® Psychotropic test includes testing for genetic polymorphisms of UGT1A4 and UGT2B15.
CNSDose® test includes testing for genetic polymorphisms of UGT1A1.
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