Human macrophages carry active CYP3A4, and cocaine boosts its activity
- Monocyte-derived macrophages from many donors expressed CYP3A4 with measurable activity, but mRNA, protein and enzyme activity correlated poorly across donors.
- Cocaine raised catalytic activity in every donor, to a level comparable with rifampicin, though its effect on expression varied.
- In rhesus macaques, cocaine coincided with lower tissue antiretroviral levels and higher CYP3A4 and PXR expression.
💡 Points Based on the abstract
Expression-function discordance is a useful warning that mRNA or protein levels alone can mislead in this tissue. If cocaine induces CYP3A4 in the very cells that harbor HIV, tissue-level antiretroviral exposure could fall below what plasma PK suggests, and that is a drug-drug interaction I'd want modeled. The macaque link is correlative so far, and I'd like to see tissue concentrations tied directly to the macrophage effect.