Pharmacogenomics and Pregnancy Pharmacokinetics: Toward Precision Drug Therapy in Obstetrics

Background: Pregnancy profoundly reshapes drug disposition through physiologic changes in absorption, distribution, metabolism, and excretion. Maternal, placental, and fetal genomes add additional layers of variability, creating challenges for safe and effective pharmacotherapy in obstetrics. Objective: To synthesize current evidence on how pharmacogenomics and pregnancy related pharmacokinetics can be integrated to optimize drug therapy in obstetrics, and to highlight clinical, safety, and research implications. Methodology: This narrative review draws from clinical guidelines (e.g., CPIC, ACOG, FDA), systematic assessments, pharmacokinetic and pharmacogenomic studies, and implementation reports. Key therapeutic domains were examined, including analgesia/anesthesia, antiepileptics, antimicrobials, and antidepressants, with a focus on pregnancy induced pharmacokinetic remodeling and genotype driven variability. Results: Pregnancy increases CYP2D6 and CYP3A activity, decreases CYP1A2 activity, and enhances glucuronidation, leading to altered drug exposure that may mask or amplify pharmacogenomic effects. Clinically, CYP2D6 genotype significantly impacts opioid safety in the peripartum and lactation period, while HLA-B15:02 and HLA-A31:01 genotypes strongly predict carbamazepine/oxcarbazepine induced cutaneous reactions. NAT2 polymorphisms modify isoniazid metabolism and toxicity risk, while CYP2C9 and UGT variants influence sulfamethoxazole exposure. CYP2C19 and CYP2D6 variants affect antidepressant efficacy and tolerability, with pregnancy further altering drug clearance. Implementation studies demonstrate that pre-emptive pharmacogenomic testing (e.g., HLA genotyping in Thailand) reduces adverse outcomes, while clinical decision support tools facilitate translation into practice. Conclusion: Pharmacogenomics, when combined with the physiologic realities of pregnancy and lactation, provides a pathway toward precision pharmacotherapy in obstetrics. High-value opportunities already exist, including avoidance of CYP2D6-dependent prodrugs in breastfeeding and pre-emptive HLA testing for carbamazepine/oxcarbazepine. Future priorities include integrating maternal–placental–fetal genomics, developing pregnancy-specific dosing algorithms, and ensuring equitable implementation across diverse populations.