Bupropion hydroxylation

CYP2B6 Bupropion hydroxylation 61-168 EEC 2.5 Methyl-phenyl-ethyl 10 pM ... 

Hesse LM, He P, Krishnaswamy S, Hao Q, Hogan K, von Moltke LL, Greenblatt DJ, Court MH. Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes. Pharmacogenetics 2004 14 225-238. 

Faucette SR, Hawke RL, Lecluyse EL, et al. Validation of bupropion hydroxylation as a selective marker of human cytochrome P450 2B6 catalytic activity. Drug Metab Dispos 2000 28 1222-1230. 

Turpeinen M, Nieminen R, Juntunen T, et al. Selective inhibition of CYP2B6-catalyzed bupropion hydroxylation in human liver microsomes in vitro. Drug Metab Dispos 2004 32 626-631. 

Turpeinen M, Tolonen A, Uusitalo J, et al. Effect of clopidogrel and ticlopidine on cytochrome P450 2B6 activity as measured by bupropion hydroxylation. Cbn Pharmacol Ther 2005 77 553-559. 

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). 

Bupropion, hydroxylation 1618 Burkitfs lymphoma cell 1029 Butyrophilin 1205 Butyrylcholinesterase 870 Buzerelin 1376... 

B6 (iS)Mephenytoin Af-demethylation 7-Ethoxy-4-trifluoromethylcoumarin 0-deethylation" Bupropion hydroxylation Phenobarbital 2- Isopropenyl-2-methyladamantane 3- Isopropenyl-3-methyldiadamantane Triethylenethiophosphoramide" Ticlopidine Clopidogrel 5-Mephenytoin "... 

Bupropion hydroxylation of the tert-butyl group to hydroxypropion is mediated almost exclusively by CYP2B6 and, to a lesser extent, by CYP2E1 (74). Other metabolites include reduction of the aminoketone to amino-alcohol isomers, threo-hydrobupropion and erythro-hydrobupropion (Fig. 21.21). Further oxidation of the bupropion side chain results in the formation of m-chlorobenzoic acid, which is eliminated in the urine as its glycine conjugate. Hydroxybupropion is approximately 50% as potent as bupropion, whereas threo-hydrobupropion and erythro-hydrobupropion have 20% of the potency of bupropion. Peak plasma concentrations for hydroxybupropion are approximately 10 times the peak level of the parent drug at steady state, with an elimination half-life of approximately 20 hours. The times to... 

The reduction in bupropion hydroxylation is due to inhibition of its cytochrome P450 isoenzyme CYP2B6-mediated metabolism by elopidogrel or ticlopidine. ... 

Fan, L., J.-C. Wang, F. Jiang, et al. 2009. Induction of cytochrome P450 2B6 activity by the herbal medicine baicalin as measured by bupropion hydroxylation. Eur. J. Clin. Pharmacol. 65 403-409. 

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