BackgroundIn pregnant women, CYP3A activity increases by ~2 fold during the third trimester (T3) [1]. Due to logistical and ethical constraints, the magnitude of CYP3A induction during the first and second trimesters (T1 and T2, respectively) is unknown. We have shown that the combination of five pregnancy‐related hormones (PRHs), cortisol(C), estradiol (E2), progesterone (P), growth hormone (GH), and placental growth hormone (PGH), at their observed T3 plasma concentrations, induced CYP3A activity in human hepatocytes to an extent comparable to that observed in vivo. Amongst these PRHs, only C consistently and significantly induced CYP3A activity [2].ObjectivesUsing human hepatocytes: 1) confirm C is the major CYP3A inducer during T1 and T2; 2) predict the magnitude of induction of CYP3A activity during T1 and T2 .MethodsSandwich cultured human hepatocytes from 3 premenopausal donors were incubated for 72h with 1X or 10X T1, T2, or T3 plasma concentrations of PRHs (adjusted for depletion). CYP3A activity was measured by 1'‐OH‐midazolam formation.ResultsAt 1X T1, T2, or T3 concentrations: 1) C consistently and significantly induced CYP3A activity; 2) induction of CYP3A activity by C or PRHs was not significantly different.ConclusionsC is the major inducer of CYP3A activity during T1‐T3. Based on these data, we predict that the magnitude of CYP3A induction during T1 and T2 will be similar to that observed during T3. This prediction is consistent with the similar increase in oral clearance of indinavir (CYP3A cleared drug) observed during T2 and T3 [3].AcknowledgementSupported by NIH grant P01DA032507