Ifosfamide Bupropion

FIGURE 4.9 Structures of the CYP2B6 substrates, cyclophosphamide, ifosfamide, propofol, bupropion, and their metabolites. 

Aflatoxin Bl, bupropion, cyclophosphamide, dexamethasone, etoposide, ifosfamide, midazolam, phenobarbital, propofol, rifampin, teitiposide, thiotepa, vitamin D, xenobiotics Amitriptyhne, carisoprodol,... 

B6 Artemisinin, bupropion, cyclophosphamide, efavirenz, ifosfamide, ketamine, S-mephobarbital, S-mephenytoin (/V-demethylation to nirvanol), methadone, nevirapine, propofol, selegiline, sertraline, ticlopidine Phenobarbital, cyclophosphamide Ticlopidine, clopidogrel... 

CYP2B6 is present at low level (< 1 %) in the liver. It catalyzes bupropion hydroxylation, S-mephenytoin N-demethylation, is involved in the metabolism of cyclophosphamide, ifosfamide, mianserin and propofol. CYP2B6 6 has been associated with reduced bupropion clearance in vitro (Hesse 2004), but not in vivo whereas a moderate clearance increase was observed with CYP2B6 4 (Kirchheiner 2003). Bupropion (150 mg dose) has been proposed for phenotyping, but it is recommended to adjust dose based on subject weight (Faucette 2000). 

The manufaeturers advise eaution if bupropion is used with drugs such as clopidogrel, cyclophosphamide, ifosfamide, orphenadrine, and ticlopi-dine as bupropion is metabolised to its major metabolite hydroxybupropi-on by CYP2B6 and these drugs are also metabolised by this isoenzyme. - However, there is no evidence to suggest that this is a problem in practice. 

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