Journal
JOURNAL OF CLINICAL PHARMACOLOGY
Volume 61, Issue 9, Pages 1149-1155Publisher
WILEY
DOI: 10.1002/jcph.1873
Keywords
ABCB1; OCT1; OPRM1; P-glycoprotein; pharmacogenomics
Categories
Funding
- National Institute on Minority Health and Health Disparities of the National Institutes of Health [G12MD007597]
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Morphine is an opioid analgesic used to treat acute and chronic moderate to severe pain, primarily by activating mu-opioid receptors. Metabolized in the liver via glucuronidation by the enzyme uridine diphosphate glucuronosyltransferase family 2 member B7, morphine also interacts with organic cation transporter isoform 1 and P-glycoprotein during distribution throughout the body. Variations in genes impacting the pharmacokinetics or pharmacodynamics of morphine can lead to different treatment outcomes for individuals.
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.
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