Defending chlorzoxazone as a CYP2E1 marker against CYP1A1 claims

  • A rebuttal to a 2026 Supersomes study that attributed chlorzoxazone 6-hydroxylation mainly to hepatic CYP1A1 rather than CYP2E1.
  • The authors revisit older literature they say the critics overlooked, which already dealt with these selectivity objections.
  • Their conclusion is that the reaction remains a dependable CYP2E1 activity readout for assessing drug interaction risk.
💡 Points Based on the abstract

Rebutting a Supersomes result with older literature is the right instinct: recombinant systems tell you what an enzyme can do, not what it does in liver. Abundance and kinetics scaling decide that. Still, a probe is only as good as its last inhibitor-based validation, so I'd want 6-hydroxylation confirmed with CYP2E1 inhibition in microsomes before trusting it in any new DDI design.

Review of the selectivity of chlorzoxazone 6-hydroxylation as a probe for human cytochrome P450 2E1 ↗