Clinical Therapeutics in Pregnancy

Table 4

Pregnancy-induced enzyme-specific changes.

Enzyme	Pregnancy-induced change	Potential substrates in obstetrics	Possible clinical consequences	Ref.
CYP3A4	Increased	Nifedipine, methadone, indinavir	Significantly 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	[107–110]
CYP2D6	Increased	Metoprolol, dextromethorphan, paroxetine, duloxetine, fluoxetine, citalopram	Increased metabolism of fluoxetine desmethylcitalopram,; lower plasma levels of the drug are associated with recurring symptoms of depression	[107, 111]
CYP1A2	Decreased	Theophylline, clozapine, olanzapine, ondansetron, cyclobenzaprine	Increase in theophylline half-life during pregnancy requiring dose reductions to avoid toxicity	[107, 112–114]
UGT1A4	Increased	Lamotrigine	Significant decrease in lamotrigine concentration resulting in loss of seizure control, recommended to measure plasma lamotrigine concentrations during each trimester and adjusting dose as needed	[115–117]
UGT1A1	Increased	Acetaminophen	Increased acetaminophen glucuronidation resulting in decreased half-life,; clinical consequences are unknown	[118]
NAT2	Decreased	Caffeine	Decreased metabolism of caffeine Clinical consequences are unknown	[114, 119, 120]