Table 4: Pregnancy-induced enzyme-specific changes.

EnzymePregnancy-induced changePotential substrates in obstetricsPossible clinical consequencesRef.

CYP3A4IncreasedNifedipine, methadone, indinavirSignificantly lower trough levels of methadone during pregnancy associated with symptoms of withdrawal. Increase daily dose by 5–10 mg or administer in more frequent doses to avoid withdrawal [107110]

CYP2D6IncreasedMetoprolol, dextromethorphan, paroxetine, duloxetine, fluoxetine, citalopramIncreased metabolism of fluoxetine desmethylcitalopram,
lower plasma levels of the drug are associated with recurring symptoms of depression
[107, 111]

CYP1A2DecreasedTheophylline, clozapine, olanzapine, ondansetron, cyclobenzaprineIncrease in theophylline half-life during pregnancy requiring dose reductions to avoid toxicity [107, 112114]

UGT1A4IncreasedLamotrigineSignificant decrease in lamotrigine concentration resulting in loss of seizure control, recommended to measure plasma lamotrigine concentrations during each trimester and adjusting dose as needed [115117]

UGT1A1IncreasedAcetaminophenIncreased acetaminophen glucuronidation resulting in decreased half-life,
clinical consequences are unknown

NAT2DecreasedCaffeineDecreased metabolism of caffeine Clinical consequences are unknown [114, 119, 120]