The study, conducted by the Washington University School of Medicine in St. Louis, looked at something called "CYP2B6 Polymorphisms" amongst the study participants. CYP2B6, or Cytochrome P450 2B6, is a specific gene in humans that happens to be responsible for the metabolization of certain substances, such as Nicotine, Diazepam and Ketamine. It just so happens that this study determined the CYP2B6 gene is also responsible for governing Methadone clearance, metabolism and plasma concentrations.
The CYP2B6 Gene has several different variants, and it is these specific variants that can impact how Methadone is metabolized differently amongst patients. The study employed 'tandem mass spectrometry to determine the plasma and urine methadone and metabolite concentrations,' and used single doses of both oral and intravenous S- and R-Methadone.
The gene variations significantly impacted the rate of clearance with both S- and R-Methadone, with the 'average S-methadone apparent oral clearance being 35 and 45% lower in CYP2B6*1/*6 and CYP2B6*6/*6 genotypes, compared to those with the CYP2B6*1/*1 variations. With R-Methadone, the oral clearance was '25 and 35% lower in CYP2B6*1/*6 compared with CYO2B6*1/*1'. Both R- and S-Methadone oral clearance was 3 and 4 times greater in those who carried the CYP2B6*4 variation. Both oral and intravenous methadone metabolism was found to be "significantly lower in CYP2B6*6 carriers compared with that of CyP2B6*1 homozygotes and greater in CYP2B6*4 carriers." It was also determined that the CYP2B6*6 genetic polymorphism found in African Americans resulted in lower metabolism and clearance of methadone.
This study gives us insight into the variation of Methadone metabolism amongst different patients, and has the potential to help influence and target treatment in relation to the each patients genes. By determining which CYP2B6 polymorphism a patient has, it makes it possible to identify those who may be at risk of overdose, as well as those who may metabolize the drug slower, allowing for treatment that is specifically catered to each patient.