Cyclophosphamide Bupropion

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... 

Atrazine, bupropion, cyclophosphamide, dextromethorphan, dextromethorphan, diazepam, dibenzo[a,h]anthracene, halothane, lidocaine, (S)-mephenytoin, (S)- and (i )-mianserin, nicotine, testosterone... 

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

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). 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

CYP2B6 <5 1-2 Bupropion Carbamazepi ne Cyclophosphamide Selegiline Flunitrazepam Meperidine Bupropion Selegiline Ethinylestradiol Phencyclidine Tamoxifen Ticlopidine Clotrimazole Carbamazepine Phenobarbital Phenytoin Pioglitazone Rifampin Troglitazone Valproic acid Ritonavir... 

Potential interactions between bupropion and cyclophosphamide (affected by CYP2B6) may be expected. 

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. 

---