Dr. Christopher Horvat Publishes Novel Pharmacogenomic Study on Sedation in Children

Dr. Christopher Horvat, one of the Safar Center’s T32 Postdoctoral Research Fellows, recently published an article titled “ABCB1 Genotype is Associated with Fentanyl Requirements in Critically Ill Children” in the journal Pediatric Research. The current approach to providing sedation and treating pain in critically ill children is guided largely by clinical response.  Medications such as fentanyl, a potent opioid, are titrated to patient response.  Some patients require modest medication doses for comfort and safety in the intensive care unit (ICU), while others require much larger doses. Foreknowledge of an individual child’s response to sedation/pain medications would reduce complications. ABCB1 is a gene that encodes p-glycoprotein, a transporter protein present in multiple sites of drug passage and metabolism such as the blood-brain-barrier, liver and kidney. In his study that included hospitalized children who received a fentanyl infusion while admitted to an ICU, de-identified drug administration data from the electronic health record were paired with patient DNA.  A significant association was identified between the amount of fentanyl administered to patients and their ABCB1 genotype.  Patients with a specific single nucleotide polymorphism at ABCB1 required 25% less fentanyl vs. patients with the more common genotype. This represents a step towards developing personalized sedation and pain medication regimens for hospitalized critically ill children. Dr. Horvat was supported by the NICHD for this research, and was mentored by Drs. Robert Clark and Philip Empey.