(845) Leveraging Pharmacogenomic Data for Methadone Dosing in Pregnancy

Friday, January 31, 2025

10:30 AM – 12:30 PM

Submitting Author and Presenting Author(s)

Megan B. Raymond, MD

OBGYN Resident Physician PGY-4
Thomas Jefferson University
Philadelphia, PA, United States

Coauthor(s)

DH

Dennis Hand, PhD

Faculty
Jefferson Center for Maternal Addiction Treatment Education and Research
Philadelphia, Pennsylvania, United States
MT

Michael Tarallo, BA

Research Coordinator
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
WK

Walter Kraft, MD

Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
Rupsa C. Boelig, MD, MS

Assistant Professor
Sidney Kimmel Medical College, Thomas Jefferson University
Philadelphia, Pennsylvania, United States

Objective: Opioid use disorder (OUD) in pregnancy remains a significant cause of maternal/infant morbidity in the United States, making appropriate OUD treatment in pregnancy critical. Pregnancy increases methadone metabolism, and studies in non-pregnant adults demonstrate that CYP2B6 genetic variants are associated with altered methadone metabolism. Current protocols for methadone management in pregnancy do not take into consideration the potential impact of CYP2B6 phenotype, and data on how CYP2B6 phenotype impacts methadone dosing in pregnancy are lacking.

Study Design: This is a prospective study of pregnant patients with OUD admitted for inpatient methadone stabilization. Methadone stabilization followed a standardized protocol involving withdrawal assessments every four hours, as-needed methadone doses based on withdrawal scores, and daily dose increases until stability. Participants underwent sampling for a pharmacologic study, collection of medical history and details of dosing through hospitalization, and CYP2B6 genotyping. CYP2B6 phenotype was characterized as either rapid metabolizer or not (slow, intermediate or normal). Primary outcome was final dose at discharge.

Results: Of N=40 enrolled, 29 had successful genotyping (Table 1), and 3/29 (10%) were rapid metabolizers. Rapid metabolizers had a higher mean dose at discharge, although this was not statistically significant (177+/-90mg vs 125mg +/-75mg, mean difference 52mg (-43mg to 147mg), p=0.27). These results were results similar when restricted to participants in the 2^nd trimester. Two patients who were rapid metabolizers left against medical advice prior to stable dose. The last dose they received was used for analysis.

Conclusion: Pregnant patients treated for OUD with a CYP2B6 rapid metabolizer phenotype had a trend toward a higher mean dose of methadone than non-rapid metabolizers; although our cohort was underpowered for statistical significance. This may support an impact of CYP2B6 genotype on methadone systemic exposure, which has implications for optimizing dosing protocol in pregnancy.