Cyclophosphamide CYP2B6 metabolism

A prodrag is a drug that is not by itself pharmacologically active but needs metabolic activation by an enzyme. Examples are the cytostatic cyclophosphamide, which is activated by hydroxylation catalyzed by CYP2B6, or HMGCoA reductase inhibitor, lovastatin, which contains... 

Bupropion is metabolized primarily by CYP2B6, and its metabolism may be altered by drugs such as cyclophosphamide, which is a substrate of 2B6. The major metabolite of bupropion, hydroxybupropion, is a moderate inhibitor of CYP2D6 and so can raise desipramine levels. Bupropion should be avoided in patients taking MAOIs. 

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). 

Rifampicin is an inducer of the cytochrome P450 isoenzymes CYP3A4 and CYP2B6, which are involved in the metabolism of cyclophosphamide and ifosfamide (see also Cyclophosphamide or Ifosfamide + Barbiturates , p.623). In the clinical study cited, rifampicin did not have a positive effect on the proportion of ifosfamide undergoing activation. In addition, since rifampicin increased metabolism overall, there is the possibility of decreased efficacy, although this remains to be shown. 

Helsby N, Tingle M (2011) The importance of correct assignment of CYP2B6 genetic variants with respect to cyclophosphamide metabolizer status. Am J Hematol 86 383-384... 

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