PsychoTropical Research - Dr Ken Gillman, Serotonin Syndrome, Mirtazapine, Dual Action Drugs. Cytochrome P450 enzymes - 2B group.

PsychoTropicalResearch, serotonin and serotonin syndrome research.

Cytochrome P450 enzymes - 2B group

Cytochrome P450 enzymes - 2B group

2B6 metabolises bupropion to it's metabolites.

Inhibitors

[IC-50 values in micro mol]:--

  • nor-orphenadrine 0.013
  • tamoxifen 0.3
  • cyclophosphamide
  • ifosfamide
  • miconazole K(i), 0.05 microM; sulconazole K(i), 0.04 microM) = high affinity

Antidepressants

IC(50) values (microM) for inhibition of bupropion hydroxylation:--

  • paroxetine (1.6), fluvoxamine (6.1), sertraline (3.2), desmethyl sertraline (19.9)
  • fluoxetine (59.5), norfluoxetine (4.2), and nefazodone (25.4).
  • propriptyline 0.093
  • nortriptyline 0.24
  • desipramine 0.18

These may be sufficient to cause significant interactions.

  • non-nucleoside reverse transcriptase inhibitors and viral protease inhibitors
  • nelfinavir 2.5
  • ritnavir 2.2
  • efavirenz 5.5

above potencies indicate potential for clinically significant interactions.

Weakly (probably not clinically significant):--

  • indinavir, saquinavir, amprenavir, delavirdine, and nevirapine.

Substrates

  • 7-ethoxy-4-trifluoromethylcoumarin deethylation (marker)
  • propofol
  • mephenytoin (N-demethylation)
  • ketamine (N-demethylation)
  • testosterone (16beta-hydroxylation)
  • selegiline

Inducers

  • nicotine ( CYP2B1/2B2 only?)

The CYP2B6 gene is directly regulated by PXR and further establish this receptor as a key regulator of drug-metabolizing P450s.

Misc

Inhibition of CYP2B6 by non-nucleoside reverse transcriptase inhibitors and viral protease inhibitors was studied in vitro in human liver microsomes using bupropion hydroxylation as the CYP2B6 index reaction. Mean IC(50) values (microM) for inhibition of bupropion hydroxylation were: nelfinavir (2.5), ritonavir (2.2), and efavirenz (5.5). The reaction was only weakly inhibited by indinavir, saquinavir, amprenavir, delavirdine, and nevirapine.

The data strongly indicate that the high extent of interindividual variation seen in vivo for selegiline clearance is caused by the metabolism of the compound by the highly polymorphic CYP2B6 and CYP2C19.