Pharmacogenomics and Morphine.

Morphine is an opioid analgesic indicated in the treatment of acute and chronic moderate to severe pain. From a pharmacodynamic standpoint, morphine exerts its effects by agonizing mu-opioid receptors predominantly, resulting in analgesia and sedation. Pharmacokinetically, morphine is primarily metabolized in the liver via glucuronidation by the enzyme uridine diphosphate glucuronosyltransferase family 2 member B7 and encounters the transporter proteins organic cation transporter isoform 1 and P-glycoprotein (adenosine triphosphate-binding cassette subfamily B member 1) as it is being distributed throughout the body. The genes coding for the proteins impacting either the pharmacokinetics or pharmacodynamics of morphine may bear genetic variations, also known as polymorphisms, which may alter the function of the proteins in such a manner that an individual may have disparate treatment outcomes. The purpose of this review is to highlight some of the genes coding for proteins that impact morphine pharmacokinetics and pharmacodynamics and present some treatment considerations.

Pharmacogenomics and Opioid Use Disorder: Clinical Decision Support in an African American Cohort.

Opioid use disorder (OUD) constitutes a significant public health burden as opioid overdose deaths have continued to rise in the United States. Although treatment modalities are available to manage OUD, some patients experience challenges achieving their OUD management goals. Some of these challenges may be attributable to inherited genetic variations, or polymorphisms, on the genes that code for proteins impacting the pharmacokinetics or pharmacodynamics of medications used in OUD management. Clinical pharmacogenomics testing can elucidate these polymorphisms; however, a lack of real-world evidence for the use of pharmacogenomics in OUD management complicates the implementation process. We conducted a retrospective cohort study of 113 patients undergoing buprenorphine-based OUD management in Northeast Washington D.C. to determine if clinical pharmacogenomics testing for CYP3A4 and CYP3A5 would impact treatment outcomes. Data were collected from the electronic medical record (EMR) from December 30, 2015 to December 31, 2016. Study outcomes were based on presence of withdrawal symptoms, instances of unauthorized substances in urine drug tests (UDTs), and sublingual buprenorphine/naloxone (SBN) dose with standard-of-care (SOC) dosing versus pharmacogenomics (PGx)-based dosing. Pearson correlation tests, Wilcoxon signed rank tests, Wilcoxon rank sum tests, and one-way ANOVA tests were used. Linear and logistic regression analyses were used to assess predictors of withdrawal symptomatology. Kaplan-Meier survival analyses were used to assess time to first withdrawal. Our research suggests that patients with at least one copy of the CYP3A4*1B allele exhibit an accelerated rate of metabolism compared to the wild-type allele CYP3A4*1.

Pharmacogenomics-guided policy in opioid use disorder (OUD) management: An ethnically-diverse case-based approach.

INTRODUCTION: Opioid use disorder (OUD) is characterized by a problematic pattern of opioid use leading to clinically-significant impairment or distress. Opioid agonist treatment is an integral component of OUD management, and buprenorphine is often utilized in OUD management due to strong clinical evidence for efficacy. However, interindividual genetic differences in buprenorphine metabolism may result in variable treatment response, leaving some patients undertreated and at increased risk for relapse. Clinical pharmacogenomics studies the effect that inherited genetic variations have on drug response. Our objective is to demonstrate the impact of pharmacogenetic testing on OUD management outcomes. METHODS: We analyzed a patient who reported discomfort at daily buprenorphine dose of 24 mg, which was a mandated daily maximum by the pharmacy benefits manager. Regular urine screenings were conducted to detect the presence of unauthorized substances, and pharmacogenetic testing was used to determine the appropriate dose of buprenorphine for OUD management. RESULTS: At the 24 mg buprenorphine daily dose, the patient had multiple relapses with unauthorized substances. Pharmacogenetic testing revealed that the patient exhibited a cytochrome P450 3A4 ultrarapid metabolizer phenotype, which necessitated a higher than recommended daily dose of buprenorphine (32 mg) for adequate OUD management. The patient exhibited a reduction in the number of relapses on the pharmacogenetic-based dose recommendation compared to standard dosing. CONCLUSION: Pharmacogenomic testing as clinical decision support helped to individualize OUD management. Collaboration by key stakeholders is essential to establishing pharmacogenetic testing as standard of care in OUD management.