personalized medicine in obstetric

Personalized medicine seeks to identify the right dose of the right drug for the right patient at the right time. Typically, individualization of therapy is based on the pharmacogenomic make-up of the individual and environmental factors that alter drug disposition and response. In addition to these factors, during pregnancy a woman’s body undergoes many changes that can impact the therapeutic efficacy of medications. Yet, there is minimal research regarding personalized medicine in obstetrics. Adoption of pharmacogenetic testing into the obstetrical care is dependent on evidence of analytical validity, clinical validity, and clinical utility. Here, briefly present information regarding the potential utility of personalized medicine for treating the obstetric patient for pain with narcotics, hypertension, and preterm labor and discuss the impediments of bringing personalized medicine to the obstetrical clinic.Obstetrics is a discipline focused on the care of women during pregnancy, an inherently normal phase of life. Unlike other medical specialties, obstetric care providers oversee a natural process which has been successfully navigated by women for thousands of years, even before modern medicine. Over time, care for the patient with abnormal pregnancy or medical complications of pregnancy has been added to the spectrum of care provided by obstetricians. These conditions are often corrected through procedural interventions on the mother or fetus, or through medical management.Beyond medications used for obstetric indications, pregnant women are also exposed to treatments for medical co-morbidities complicating pregnancy. The selection of a medication to treat a given pathology) rests on evidence of efficacy in the non-pregnant population, balanced against teratogenicity or correlation with poor obstetric outcomes. Historically, the FDA has maintained a pregnancy drug rating system to summarize the known information on risk of drug usage in pregnancy. This A-B-C-D-X letter rating has been misinterpreted by many clinicians and has led to the withholding of therapy due to the perceived risk of medications within specific classes3. As early as 1997, the FDA recommended changes in drug labeling to move towards a descriptive rating system to encourage clinicians to more carefully consider the evidence supporting the use of a drug in pregnancy4Peripartum pain is commonly treated by narcotic pain relievers, such as codeine and hydrocodone. These prodrugs require biotransformation through CYP2D6 metabolism to their active moieties, morphine and hydromorphone, respectively. CYP2D6 activity is induced during pregnancyIn addition, more than 80 pharmacogenomic variants have been reported for CYP2D6 (many of which alter the activity of the enzyme (Approximately 7% of Caucasians have a variant that leads to a CYP2D6 poor metabolizer (PM) phenotype, which results in reduced enzyme activity. For instance, these individuals have reduced capacity to convert codeine to morphine and do not obtain adequate pain relief from codeine. Conversely, about 2–3% of Caucasians possess multiple copies of active CYP2D6 alleles, leading to an ultrarapid metabolism (UM) phenotype. In these individuals, codeine is rapidly converted to morphine, potentially leading to toxicity. While rare, cases of death in UM individuals treated with clinical doses of codeine have been reported. In some of these individuals, the presence of a variant that reduces the activity of UDP-Glucuronosyltransferase-2B7 (UGT2B7), the enzyme responsible for inactivation of morphine, may have also contributed to the toxic concentrations of morphine. After the report of an infant death associated with the CYP2D6 UM genotype of a breastfeeding mother taking codeine for post-Cesarean pain relief21, the U.S. FDA issued a Public Health Advisory cautioning women on the use of narcotic analgesics during breastfeeding22. Additionally, the Clinical Pharmacogenomics Implementation Consortium (CPIC) has issued guidelines on the use of codeine with respect to CYP2D6 genotype. While hydrocodone and oxycodone undergo similar metabolic activation via CYP2D6, there are not adequate data regarding the consequences of PM or UM phenotype for use of these agents.

Keywords:

personalized medicine , pharmacogenetic , narcotic , CYP2D6