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.