Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun 1;24(3):18.
doi: 10.1038/s41397-024-00339-w.

Pharmacokinetic and neuroimmune pharmacogenetic impacts on slow-release morphine cancer pain control and adverse effects

Daniel T Barratt  1   2 , Pål Klepstad  3   4 , Ola Dale  3 , Stein Kaasa  5 , Andrew A Somogyi  6   7
Affiliations

Pharmacokinetic and neuroimmune pharmacogenetic impacts on slow-release morphine cancer pain control and adverse effects

Daniel T Barratt et al. Pharmacogenomics J. .

Abstract

The aim was to determine if opioid neuroimmunopharmacology pathway gene polymorphisms alter serum morphine, morphine-3-glucuronide and morphine-6-glucuronide concentration-response relationships in 506 cancer patients receiving controlled-release oral morphine. Morphine-3-glucuronide concentrations (standardised to 11 h post-dose) were higher in patients without pain control (median (interquartile range) 1.2 (0.7-2.3) versus 1.0 (0.5-1.9) μM, P = 0.006), whereas morphine concentrations were higher in patients with cognitive dysfunction (40 (20-81) versus 29 (14-60) nM, P = 0.02). TLR2 rs3804100 variant carriers had reduced odds (adjusted odds ratio (95% confidence interval) 0.42 (0.22-0.82), P = 0.01) of opioid adverse events. IL2 rs2069762 G/G (0.20 (0.06-0.52)), BDNF rs6265 A/A (0.15 (0.02-0.63)) and IL6R rs8192284 carrier (0.55 (0.34-0.90)) genotypes had decreased, and IL6 rs10499563 C/C increased (3.3 (1.2-9.3)), odds of sickness response (P ≤ 0.02). The study has limitations in heterogeneity in doses, sampling times and diagnoses but still suggests that pharmacokinetics and immune genetics co-contribute to morphine pain control and adverse effects in cancer patients.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Summary of pharmacogenomic (innate immune, neuronal, neurotrophic) and pharmacokinetic (plasma morphine and -3 and 6-glucuronides), patient and treatment centre factors contributing to pain control and adverse effects in cancer patients receiving sustained-release morphine.
+ refers to a positive contribution; - refers to negative contribution.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Wiffen P, Wee B, Derry S, Bell R, Moore R. Opioids for cancer pain - an overview of Cochrane reviews. Cochrane Database Syst Rev. 2017;7:CD012592. - PMC - PubMed
    1. Hutchinson MR, Zhang Y, Shridhar M, Evans JH, Buchanan MM, Zhao TX, et al. Evidence that opioids may have toll-like receptor 4 and MD-2 effects. Brain Behav Immun. 2010;24:83–95. doi: 10.1016/j.bbi.2009.08.004. - DOI - PMC - PubMed
    1. Lewis SS, Hutchinson MR, Rezvani N, Loram LC, Zhang Y, Maier SF, et al. Evidence that intrathecal morphine-3-glucuronide may cause pain enhancement via toll-like receptor 4/MD-2 and interleukin-1beta. Neuroscience. 2010;165:569–83. doi: 10.1016/j.neuroscience.2009.10.011. - DOI - PMC - PubMed
    1. Somogyi AA, Musolino ST, Barratt DT. New pharmacological perspectives and therapeutic options for opioids: Differences matter. Anaesth Intensive Care. 2022;50:127–40. doi: 10.1177/0310057X211063891. - DOI - PubMed
    1. Andersen G, Christrup L, Sjogren P. Relationships among morphine metabolism, pain and side effects during long-term treatment: an update. J Pain Symptom Manage. 2003;25:74–91. doi: 10.1016/S0885-3924(02)00531-6. - DOI - PubMed

MeSH terms

-