Clinical Importance of Pharmacogenomics for Codeine Dosing: An analysis of Codeine Metabolism within Arab Populations
Faculty Mentor
Ahmed Abu Fayyad
Major/Area of Research
Pharmaceuticals
Description
NTRODUCTION: Codeine is an analgesic that requires metabolic activation to have its full effect. However, its efficacy and safety depend on the rate at which codeine is converted into its metabolite, morphine. The extent to which one metabolizes codeine is dependent on their genetic disposition. Ultra-rapid metabolizers convert higher levels of codeine into morphine, increasing the risks of opioid intoxication. Arab populations across MENA have been observed to have a high prevalence of ultra-rapid metabolizers. The objective of this review is to highlight the importance of pharmacogenomics when determining codeine dosing, especially for Arabs who may be susceptible to ultra-rapid metabolism.
METHOD: A literature-based search was conducted to gather information on codeine metabolism in the Arab population, using the key search terms of codeine metabolism, CYP2D6 polymorphism, allele duplication, Arabs, and pharmacogenomics. This review includes original research articles that address the pharmacokinetics of codeine and CYP2D6 allele duplication in relation to Arab populations. Data from these articles analyzes the prevalence of ultra-rapid metabolizers and the associated harms of codeine use in these populations.
RESULTS: The reviewed literature demonstrates that there is a notably higher prevalence of ultra-rapid metabolizers within Arab populations across the Middle East and North Africa at 11.02%, with some countries such as Algeria having a frequency as high as 28.3%. On the contrary, the average prevalence of ultra-rapid metabolism across the rest of the world was seen to be 1.5%. As observed in the literature, ultra-rapid metabolizers are at higher risk for opioid intoxication and codeine addiction when compared to normal metabolizers. With just one dose of codeine, concentrations of morphine within ultra-rapid metabolizers were 150% the number of normal metabolizers. This issue is more concerning for vulnerable populations, such as those with underlying conditions, children, and breast-feeding mothers. There have been cases of breast-feeding mothers taking codeine who are unaware of their ultra-rapid metabolism transferring high levels of morphine to their infant, resulting in fatal respiratory depression. Concentrations of morphine within poor metabolizers (individuals with little to no metabolizing activity) were 2200% less when compared to normal metabolizers. This results in poor pain management, which in turn can develop into chronic pain.
CONCLUSION: Although pharmacogenomics in clinical practice is not yet established, the literature suggests that its application can lead to significant improvements in drug safety and efficacy. For codeine, knowing whether a patient is an ultra-rapid or poor metabolizer could mean the difference between opioid intoxication and insufficient pain management. Adopting measures to, at the very least, educate patients who may be part of a vulnerable demographic can help prevent codeine abuse. Among these vulnerable demographics, Arab populations show a significantly higher prevalence of ultra-rapid metabolism. Regulatory agencies should consider incorporating pharmacogenomic data into their guidelines to ensure safety and efficacy.
Clinical Importance of Pharmacogenomics for Codeine Dosing: An analysis of Codeine Metabolism within Arab Populations
NTRODUCTION: Codeine is an analgesic that requires metabolic activation to have its full effect. However, its efficacy and safety depend on the rate at which codeine is converted into its metabolite, morphine. The extent to which one metabolizes codeine is dependent on their genetic disposition. Ultra-rapid metabolizers convert higher levels of codeine into morphine, increasing the risks of opioid intoxication. Arab populations across MENA have been observed to have a high prevalence of ultra-rapid metabolizers. The objective of this review is to highlight the importance of pharmacogenomics when determining codeine dosing, especially for Arabs who may be susceptible to ultra-rapid metabolism.
METHOD: A literature-based search was conducted to gather information on codeine metabolism in the Arab population, using the key search terms of codeine metabolism, CYP2D6 polymorphism, allele duplication, Arabs, and pharmacogenomics. This review includes original research articles that address the pharmacokinetics of codeine and CYP2D6 allele duplication in relation to Arab populations. Data from these articles analyzes the prevalence of ultra-rapid metabolizers and the associated harms of codeine use in these populations.
RESULTS: The reviewed literature demonstrates that there is a notably higher prevalence of ultra-rapid metabolizers within Arab populations across the Middle East and North Africa at 11.02%, with some countries such as Algeria having a frequency as high as 28.3%. On the contrary, the average prevalence of ultra-rapid metabolism across the rest of the world was seen to be 1.5%. As observed in the literature, ultra-rapid metabolizers are at higher risk for opioid intoxication and codeine addiction when compared to normal metabolizers. With just one dose of codeine, concentrations of morphine within ultra-rapid metabolizers were 150% the number of normal metabolizers. This issue is more concerning for vulnerable populations, such as those with underlying conditions, children, and breast-feeding mothers. There have been cases of breast-feeding mothers taking codeine who are unaware of their ultra-rapid metabolism transferring high levels of morphine to their infant, resulting in fatal respiratory depression. Concentrations of morphine within poor metabolizers (individuals with little to no metabolizing activity) were 2200% less when compared to normal metabolizers. This results in poor pain management, which in turn can develop into chronic pain.
CONCLUSION: Although pharmacogenomics in clinical practice is not yet established, the literature suggests that its application can lead to significant improvements in drug safety and efficacy. For codeine, knowing whether a patient is an ultra-rapid or poor metabolizer could mean the difference between opioid intoxication and insufficient pain management. Adopting measures to, at the very least, educate patients who may be part of a vulnerable demographic can help prevent codeine abuse. Among these vulnerable demographics, Arab populations show a significantly higher prevalence of ultra-rapid metabolism. Regulatory agencies should consider incorporating pharmacogenomic data into their guidelines to ensure safety and efficacy.