AIMS: To assess CYP2D6 activity and genotype in a group of patients undergoing methadone maintenance treatment (MMT). METHODS: Blood samples from 34 MMT patients were genotyped by a polymerase chain reaction-based method, and results were compared with CYP2D6 phenotype (n = 28), as measured by the molar metabolic ratio (MR) of dextromethorphan (DEX)/dextrorphan (DOR) in plasma. RESULTS: Whereas 9% of patients (3/34) were poor metabolizers (PM) by genotype, 57% (16/28) were PM by phenotype (P < 0.005). Eight patients, who were genotypically extensive metabolizers (EM), were assigned as PM by their phenotype. The number of CYP2D6*4 alleles and sex were significant determinants of CYP2D6 activity in MMT patients, whereas other covariates (methadone dose, age, weight) did not contribute to variation in CYP2D6 activity. CONCLUSIONS: There was a discordance between genotype and in vivo CYP2D6 activity in MMT patients. This finding is consistent with inhibition of CYP2D6 activity by methadone and may have implications for the safety and efficacy of other CYP2D6 substrates taken by MMT patients.
AIMS: To assess CYP2D6 activity and genotype in a group of patients undergoing methadone maintenance treatment (MMT). METHODS: Blood samples from 34 MMTpatients were genotyped by a polymerase chain reaction-based method, and results were compared with CYP2D6 phenotype (n = 28), as measured by the molar metabolic ratio (MR) of dextromethorphan (DEX)/dextrorphan (DOR) in plasma. RESULTS: Whereas 9% of patients (3/34) were poor metabolizers (PM) by genotype, 57% (16/28) were PM by phenotype (P < 0.005). Eight patients, who were genotypically extensive metabolizers (EM), were assigned as PM by their phenotype. The number of CYP2D6*4 alleles and sex were significant determinants of CYP2D6 activity in MMTpatients, whereas other covariates (methadone dose, age, weight) did not contribute to variation in CYP2D6 activity. CONCLUSIONS: There was a discordance between genotype and in vivo CYP2D6 activity in MMTpatients. This finding is consistent with inhibition of CYP2D6 activity by methadone and may have implications for the safety and efficacy of other CYP2D6 substrates taken by MMTpatients.
Authors: Janet K Coller; Jennifer R Michalakas; Heather M James; Aaron L Farquharson; Joel Colvill; Jason M White; Andrew A Somogyi Journal: Br J Clin Pharmacol Date: 2012-11 Impact factor: 4.335
Authors: Lauren L Richards-Waugh; Donald A Primerano; Yulia Dementieva; James C Kraner; Gary O Rankin Journal: J Anal Toxicol Date: 2014-10 Impact factor: 3.367