Evan Minami¹*, Kory Johnson², Kaylene Au³, Douglas Johnson^3,4,5, Lisa Cook⁵, Steven Namiki³, Richard Severino⁴ and Christopher Lum^3,4

¹University of Southern California, Los Angeles, CA, USA

*Corresponding Author: Evan Minami, University of Southern California, Los Angeles, CA, USA.

Received: August 21, 2021; Published: September 30, 2021

Abstract

Best practice guidelines and the Substance Abuse and Mental Health Services Administration (SAMHSA) Treatment Improvement Protocol 63 mandates methadone maintenance induction with low initial dosage and a small, slow increase to avoid overdose and to reach a steady state. Primarily metabolized by the cytochrome 2D6 enzyme, it is shown that polymorphisms in this subunit can greatly affect the rate at which methadone is metabolized in individuals. Six genetic polymorphisms are commonly identified which ranged from poor metabolizers to ultrarapid metabolizers. Patients who can’t reach a steady state dose in a reasonable time because of slow incremental dose increases can be more susceptible to relapse and slow metabolizers can be susceptible to overdose. Phenotypic data of CYP2D6 polymorphisms can guide better initial dosing for patients that may require a higher dose to reach a steady state. To date, there has been no way to predict the dose needed for a steady state. A total of 25 patients were enrolled and genotyped with an average time on methadone of 14.2 years and ages 31 to 75 years. Ultra-rapid metabolizers were shown to require significantly higher doses of methadone to reach a steady state. This was a pilot study that supports further research into methadone pharmacogenomics.

Keywords: Methadone; Pharmacogenomics; CYP2D6

References

1. Lippold KM., et al. “Racial/Ethnic and Age Group Differences in Opioid and Synthetic Opioid-Involved Overdose Deaths Among Adults Aged ≥18 Years in Metropolitan Areas — United States, 2015-2017”. MMWR Morbidity and Mortality Weekly Report 68 (2019): 967-973.
2. Bell J and Strang J. “Medication Treatment of Opioid Use Disorder”. Biology Psychiatry1 (2020): 82-88.
3. Dickmann LJ and Isoherranen N. “Quantitative prediction of CYP2B6 induction by estradiol during pregnancy: potential explanation for increased methadone clearance during pregnancy”. Drug Metabolism and Disposition2 (2013): 270-274.
4. Dagostino C., et al. “CYP2D6 genotype can help to predict effectiveness and safety during opioid treatment for chronic low back pain: results from a retrospective study in an Italian cohort”. Pharmacogenomics and Personalized Medicine 11 (2018): 179-191.
5. Kirchheiner J., et al. “CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages”. Acta Psychiatrica Scandinavica 3 (2001): 173-192.
6. “Medications for Opioid Use Disorder SAMHSA TIP 63 - UPDATED” (2020): 3-35.
7. Dole VP and Nyswander ME. “Heroin Addiction—A Metabolic Disease”. Archives of Internal Medicine1 (1967): 19-24.
8. Dodgen T., et al. “Pharmacogenetic comparison of CYP2D6 predictive and measured phenotypes in a South African cohort”. The Pharmacogenomics Journal 16 (2016): 566-572.
9. Crews KR., et al. “Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update”. Clinical Pharmacology Therapy4 (2014): 376-382.
10. Adedeji WA., et al. “Evaluation of CYP2D6 phenotype in the Yoruba Nigerian population”. Expert Review of Clinical Pharmacology 10 (2017): 1145-1152.
11. Yee MM., et al. “Cytochrome P450 2D6 polymorphisms and predicted opioid metabolism in African American children with sickle cell disease”. Journal of Pediatric Hematology/Oncology 7 (2013): e301-305.

Citation

Citation: Evan Minami., et al. “Pharmacogenetic Analysis of Three Cytochrome P450 Gene Polymorphisms (CYP2D6, CYP3A4, and CYP3A5) in Methadone Maintenance Patients". Acta Scientific Pharmacology 2.10 (2020): 02-07.

Copyright

Copyright: © 2021 Evan Minami., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.