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Espen Molden - One of the best experts on this subject based on the ideXlab platform.

  • significantly lower cyp2d6 metabolism measured as the o n desmethylvenlafaxine Metabolic Ratio in carriers of cyp2d6 41 versus cyp2d6 9 or cyp2d6 10 a study on therapeutic drug monitoring data from 1003 genotyped scandinavian patients
    British Journal of Clinical Pharmacology, 2019
    Co-Authors: Tore Haslemo, Erik Eliasson, Marin M. Jukic, Magnus Ingelmansundberg, Espen Molden
    Abstract:

    AIMS CYP2D6*9, CYP2D6*10 and CYP2D6*41 are the most frequent reduced-function CYP2D6 alleles in Caucasians. Despite lacking in vivo evidence, they are collectively classified with an enzyme activity score of 0.5. Thus, the aim of this study was to compare the functional impact of CYP2D6*9, CYP2D6*10 and CYP2D6*41 on CYP2D6 metabolism in a large patient population. METHODS A total of 1003 patients (mainly Caucasians) with data on CYP2D6 genotype and serum concentRations of venlafaxine and metabolites were included from a therapeutic drug monitoring service in Oslo, Norway. The O-desmethyl-to-N-desmethyl-venlafaxine Metabolic Ratio (MR) was applied as CYP2D6 biomarker and compared (Mann-Whitney) between carriers of CYP2D6*9-10 (merged) and CYP2D6*41, either combined with CYP2D6*1 or non-coding (null) alleles. MR subgroup estimates were obtained by multiple linear regression for calculations of CYP2D6*9-10 and CYP2D6*41 activity scores. RESULTS MR was significantly lower in carriers of CYP2D6*41 than CYP2D6*9-10 (P < 0.002). The majority of CYP2D6*41/null carriers (86.7%) had MR in the observed range of CYP2D6null/null carriers compared with the minority of CYP2D6*9-10/null carriers (17.4%). CYP2D6 genotype explained 60.7% of MR variability in the multivariate analysis providing subgroup estimates of 9.54 (95% CI; 7.45-12.20), 3.55 (2.06-6.10), 1.33 (0.87-2.05) and 0.47 (0.35-0.61) in carriers of CYP2D6*1/null (n = 269), CYP2D6*9-10/null (n = 17), CYP2D6*41/null (n = 30) and CYP2D6null/null (n = 95), respectively. Based on these estimates, the calculated activity score of CYP2D6*41 was 0.095 compared to 0.34 for CYP2D6*9-10. CONCLUSIONS CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine Ratio is significantly lower in Scandinavian carriers of CYP2D6*41 vs. CYP2D6*9-10. Thus, these alleles should be differentiated when classifying CYP2D6 phenotype from genotype.

  • Significantly lower CYP2D6 metabolism measured as the O/N‐desmethylvenlafaxine Metabolic Ratio in carriers of CYP2D6*41 versus CYP2D6*9 or CYP2D6*10: a study on therapeutic drug monitoring data from 1003 genotyped Scandinavian patients
    British journal of clinical pharmacology, 2018
    Co-Authors: Tore Haslemo, Magnus Ingelman-sundberg, Erik Eliasson, Marin M. Jukic, Espen Molden
    Abstract:

    AIMS CYP2D6*9, CYP2D6*10 and CYP2D6*41 are the most frequent reduced-function CYP2D6 alleles in Caucasians. Despite lacking in vivo evidence, they are collectively classified with an enzyme activity score of 0.5. Thus, the aim of this study was to compare the functional impact of CYP2D6*9, CYP2D6*10 and CYP2D6*41 on CYP2D6 metabolism in a large patient population. METHODS A total of 1003 patients (mainly Caucasians) with data on CYP2D6 genotype and serum concentRations of venlafaxine and metabolites were included from a therapeutic drug monitoring service in Oslo, Norway. The O-desmethyl-to-N-desmethyl-venlafaxine Metabolic Ratio (MR) was applied as CYP2D6 biomarker and compared (Mann-Whitney) between carriers of CYP2D6*9-10 (merged) and CYP2D6*41, either combined with CYP2D6*1 or non-coding (null) alleles. MR subgroup estimates were obtained by multiple linear regression for calculations of CYP2D6*9-10 and CYP2D6*41 activity scores. RESULTS MR was significantly lower in carriers of CYP2D6*41 than CYP2D6*9-10 (P 

Erik Eliasson - One of the best experts on this subject based on the ideXlab platform.

  • significantly lower cyp2d6 metabolism measured as the o n desmethylvenlafaxine Metabolic Ratio in carriers of cyp2d6 41 versus cyp2d6 9 or cyp2d6 10 a study on therapeutic drug monitoring data from 1003 genotyped scandinavian patients
    British Journal of Clinical Pharmacology, 2019
    Co-Authors: Tore Haslemo, Erik Eliasson, Marin M. Jukic, Magnus Ingelmansundberg, Espen Molden
    Abstract:

    AIMS CYP2D6*9, CYP2D6*10 and CYP2D6*41 are the most frequent reduced-function CYP2D6 alleles in Caucasians. Despite lacking in vivo evidence, they are collectively classified with an enzyme activity score of 0.5. Thus, the aim of this study was to compare the functional impact of CYP2D6*9, CYP2D6*10 and CYP2D6*41 on CYP2D6 metabolism in a large patient population. METHODS A total of 1003 patients (mainly Caucasians) with data on CYP2D6 genotype and serum concentRations of venlafaxine and metabolites were included from a therapeutic drug monitoring service in Oslo, Norway. The O-desmethyl-to-N-desmethyl-venlafaxine Metabolic Ratio (MR) was applied as CYP2D6 biomarker and compared (Mann-Whitney) between carriers of CYP2D6*9-10 (merged) and CYP2D6*41, either combined with CYP2D6*1 or non-coding (null) alleles. MR subgroup estimates were obtained by multiple linear regression for calculations of CYP2D6*9-10 and CYP2D6*41 activity scores. RESULTS MR was significantly lower in carriers of CYP2D6*41 than CYP2D6*9-10 (P < 0.002). The majority of CYP2D6*41/null carriers (86.7%) had MR in the observed range of CYP2D6null/null carriers compared with the minority of CYP2D6*9-10/null carriers (17.4%). CYP2D6 genotype explained 60.7% of MR variability in the multivariate analysis providing subgroup estimates of 9.54 (95% CI; 7.45-12.20), 3.55 (2.06-6.10), 1.33 (0.87-2.05) and 0.47 (0.35-0.61) in carriers of CYP2D6*1/null (n = 269), CYP2D6*9-10/null (n = 17), CYP2D6*41/null (n = 30) and CYP2D6null/null (n = 95), respectively. Based on these estimates, the calculated activity score of CYP2D6*41 was 0.095 compared to 0.34 for CYP2D6*9-10. CONCLUSIONS CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine Ratio is significantly lower in Scandinavian carriers of CYP2D6*41 vs. CYP2D6*9-10. Thus, these alleles should be differentiated when classifying CYP2D6 phenotype from genotype.

  • Significantly lower CYP2D6 metabolism measured as the O/N‐desmethylvenlafaxine Metabolic Ratio in carriers of CYP2D6*41 versus CYP2D6*9 or CYP2D6*10: a study on therapeutic drug monitoring data from 1003 genotyped Scandinavian patients
    British journal of clinical pharmacology, 2018
    Co-Authors: Tore Haslemo, Magnus Ingelman-sundberg, Erik Eliasson, Marin M. Jukic, Espen Molden
    Abstract:

    AIMS CYP2D6*9, CYP2D6*10 and CYP2D6*41 are the most frequent reduced-function CYP2D6 alleles in Caucasians. Despite lacking in vivo evidence, they are collectively classified with an enzyme activity score of 0.5. Thus, the aim of this study was to compare the functional impact of CYP2D6*9, CYP2D6*10 and CYP2D6*41 on CYP2D6 metabolism in a large patient population. METHODS A total of 1003 patients (mainly Caucasians) with data on CYP2D6 genotype and serum concentRations of venlafaxine and metabolites were included from a therapeutic drug monitoring service in Oslo, Norway. The O-desmethyl-to-N-desmethyl-venlafaxine Metabolic Ratio (MR) was applied as CYP2D6 biomarker and compared (Mann-Whitney) between carriers of CYP2D6*9-10 (merged) and CYP2D6*41, either combined with CYP2D6*1 or non-coding (null) alleles. MR subgroup estimates were obtained by multiple linear regression for calculations of CYP2D6*9-10 and CYP2D6*41 activity scores. RESULTS MR was significantly lower in carriers of CYP2D6*41 than CYP2D6*9-10 (P 

  • Risperidone Metabolic Ratio as a biomarker of individual CYP2D6 genotype in schizophrenic patients
    European journal of clinical pharmacology, 2014
    Co-Authors: Buster Mannheimer, Johan Holm, Larissa Koukel, Leif Bertilsson, Urban Ösby, Erik Eliasson
    Abstract:

    Purpose The purpose of the present study was to investigate the predictive value of the risperidone Metabolic Ratio for the individual CYP2D6 genotype.

Marin M. Jukic - One of the best experts on this subject based on the ideXlab platform.

  • significantly lower cyp2d6 metabolism measured as the o n desmethylvenlafaxine Metabolic Ratio in carriers of cyp2d6 41 versus cyp2d6 9 or cyp2d6 10 a study on therapeutic drug monitoring data from 1003 genotyped scandinavian patients
    British Journal of Clinical Pharmacology, 2019
    Co-Authors: Tore Haslemo, Erik Eliasson, Marin M. Jukic, Magnus Ingelmansundberg, Espen Molden
    Abstract:

    AIMS CYP2D6*9, CYP2D6*10 and CYP2D6*41 are the most frequent reduced-function CYP2D6 alleles in Caucasians. Despite lacking in vivo evidence, they are collectively classified with an enzyme activity score of 0.5. Thus, the aim of this study was to compare the functional impact of CYP2D6*9, CYP2D6*10 and CYP2D6*41 on CYP2D6 metabolism in a large patient population. METHODS A total of 1003 patients (mainly Caucasians) with data on CYP2D6 genotype and serum concentRations of venlafaxine and metabolites were included from a therapeutic drug monitoring service in Oslo, Norway. The O-desmethyl-to-N-desmethyl-venlafaxine Metabolic Ratio (MR) was applied as CYP2D6 biomarker and compared (Mann-Whitney) between carriers of CYP2D6*9-10 (merged) and CYP2D6*41, either combined with CYP2D6*1 or non-coding (null) alleles. MR subgroup estimates were obtained by multiple linear regression for calculations of CYP2D6*9-10 and CYP2D6*41 activity scores. RESULTS MR was significantly lower in carriers of CYP2D6*41 than CYP2D6*9-10 (P < 0.002). The majority of CYP2D6*41/null carriers (86.7%) had MR in the observed range of CYP2D6null/null carriers compared with the minority of CYP2D6*9-10/null carriers (17.4%). CYP2D6 genotype explained 60.7% of MR variability in the multivariate analysis providing subgroup estimates of 9.54 (95% CI; 7.45-12.20), 3.55 (2.06-6.10), 1.33 (0.87-2.05) and 0.47 (0.35-0.61) in carriers of CYP2D6*1/null (n = 269), CYP2D6*9-10/null (n = 17), CYP2D6*41/null (n = 30) and CYP2D6null/null (n = 95), respectively. Based on these estimates, the calculated activity score of CYP2D6*41 was 0.095 compared to 0.34 for CYP2D6*9-10. CONCLUSIONS CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine Ratio is significantly lower in Scandinavian carriers of CYP2D6*41 vs. CYP2D6*9-10. Thus, these alleles should be differentiated when classifying CYP2D6 phenotype from genotype.

  • Significantly lower CYP2D6 metabolism measured as the O/N‐desmethylvenlafaxine Metabolic Ratio in carriers of CYP2D6*41 versus CYP2D6*9 or CYP2D6*10: a study on therapeutic drug monitoring data from 1003 genotyped Scandinavian patients
    British journal of clinical pharmacology, 2018
    Co-Authors: Tore Haslemo, Magnus Ingelman-sundberg, Erik Eliasson, Marin M. Jukic, Espen Molden
    Abstract:

    AIMS CYP2D6*9, CYP2D6*10 and CYP2D6*41 are the most frequent reduced-function CYP2D6 alleles in Caucasians. Despite lacking in vivo evidence, they are collectively classified with an enzyme activity score of 0.5. Thus, the aim of this study was to compare the functional impact of CYP2D6*9, CYP2D6*10 and CYP2D6*41 on CYP2D6 metabolism in a large patient population. METHODS A total of 1003 patients (mainly Caucasians) with data on CYP2D6 genotype and serum concentRations of venlafaxine and metabolites were included from a therapeutic drug monitoring service in Oslo, Norway. The O-desmethyl-to-N-desmethyl-venlafaxine Metabolic Ratio (MR) was applied as CYP2D6 biomarker and compared (Mann-Whitney) between carriers of CYP2D6*9-10 (merged) and CYP2D6*41, either combined with CYP2D6*1 or non-coding (null) alleles. MR subgroup estimates were obtained by multiple linear regression for calculations of CYP2D6*9-10 and CYP2D6*41 activity scores. RESULTS MR was significantly lower in carriers of CYP2D6*41 than CYP2D6*9-10 (P 

Tore Haslemo - One of the best experts on this subject based on the ideXlab platform.

  • significantly lower cyp2d6 metabolism measured as the o n desmethylvenlafaxine Metabolic Ratio in carriers of cyp2d6 41 versus cyp2d6 9 or cyp2d6 10 a study on therapeutic drug monitoring data from 1003 genotyped scandinavian patients
    British Journal of Clinical Pharmacology, 2019
    Co-Authors: Tore Haslemo, Erik Eliasson, Marin M. Jukic, Magnus Ingelmansundberg, Espen Molden
    Abstract:

    AIMS CYP2D6*9, CYP2D6*10 and CYP2D6*41 are the most frequent reduced-function CYP2D6 alleles in Caucasians. Despite lacking in vivo evidence, they are collectively classified with an enzyme activity score of 0.5. Thus, the aim of this study was to compare the functional impact of CYP2D6*9, CYP2D6*10 and CYP2D6*41 on CYP2D6 metabolism in a large patient population. METHODS A total of 1003 patients (mainly Caucasians) with data on CYP2D6 genotype and serum concentRations of venlafaxine and metabolites were included from a therapeutic drug monitoring service in Oslo, Norway. The O-desmethyl-to-N-desmethyl-venlafaxine Metabolic Ratio (MR) was applied as CYP2D6 biomarker and compared (Mann-Whitney) between carriers of CYP2D6*9-10 (merged) and CYP2D6*41, either combined with CYP2D6*1 or non-coding (null) alleles. MR subgroup estimates were obtained by multiple linear regression for calculations of CYP2D6*9-10 and CYP2D6*41 activity scores. RESULTS MR was significantly lower in carriers of CYP2D6*41 than CYP2D6*9-10 (P < 0.002). The majority of CYP2D6*41/null carriers (86.7%) had MR in the observed range of CYP2D6null/null carriers compared with the minority of CYP2D6*9-10/null carriers (17.4%). CYP2D6 genotype explained 60.7% of MR variability in the multivariate analysis providing subgroup estimates of 9.54 (95% CI; 7.45-12.20), 3.55 (2.06-6.10), 1.33 (0.87-2.05) and 0.47 (0.35-0.61) in carriers of CYP2D6*1/null (n = 269), CYP2D6*9-10/null (n = 17), CYP2D6*41/null (n = 30) and CYP2D6null/null (n = 95), respectively. Based on these estimates, the calculated activity score of CYP2D6*41 was 0.095 compared to 0.34 for CYP2D6*9-10. CONCLUSIONS CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine Ratio is significantly lower in Scandinavian carriers of CYP2D6*41 vs. CYP2D6*9-10. Thus, these alleles should be differentiated when classifying CYP2D6 phenotype from genotype.

  • Significantly lower CYP2D6 metabolism measured as the O/N‐desmethylvenlafaxine Metabolic Ratio in carriers of CYP2D6*41 versus CYP2D6*9 or CYP2D6*10: a study on therapeutic drug monitoring data from 1003 genotyped Scandinavian patients
    British journal of clinical pharmacology, 2018
    Co-Authors: Tore Haslemo, Magnus Ingelman-sundberg, Erik Eliasson, Marin M. Jukic, Espen Molden
    Abstract:

    AIMS CYP2D6*9, CYP2D6*10 and CYP2D6*41 are the most frequent reduced-function CYP2D6 alleles in Caucasians. Despite lacking in vivo evidence, they are collectively classified with an enzyme activity score of 0.5. Thus, the aim of this study was to compare the functional impact of CYP2D6*9, CYP2D6*10 and CYP2D6*41 on CYP2D6 metabolism in a large patient population. METHODS A total of 1003 patients (mainly Caucasians) with data on CYP2D6 genotype and serum concentRations of venlafaxine and metabolites were included from a therapeutic drug monitoring service in Oslo, Norway. The O-desmethyl-to-N-desmethyl-venlafaxine Metabolic Ratio (MR) was applied as CYP2D6 biomarker and compared (Mann-Whitney) between carriers of CYP2D6*9-10 (merged) and CYP2D6*41, either combined with CYP2D6*1 or non-coding (null) alleles. MR subgroup estimates were obtained by multiple linear regression for calculations of CYP2D6*9-10 and CYP2D6*41 activity scores. RESULTS MR was significantly lower in carriers of CYP2D6*41 than CYP2D6*9-10 (P 

Marc Ansari - One of the best experts on this subject based on the ideXlab platform.

  • p97 busulfan sulfolane Metabolic Ratio on the third day of conditioning may predict the event free survival in children receiving busulfan based conditioning prior to hematopoietic stem cell transplantation
    Archives of Disease in Childhood, 2019
    Co-Authors: Crs Uppugunduri, M A Rezgui, C P Huezodiaz, Tiago Nava, Simona Jurkovic Mlakar, Yves Theoret, Henrique Bittencourt, Maja Krajinovic, Marc Ansari
    Abstract:

    Background Busulfan (Bu) is widely used as a component of myeloablative conditioning regimen before hematopoietic stem cell transplantation (HSCT) in children. Obtaining the Ratio of Bu to its metabolite sulfolane i.e. Metabolic Ratio (MR) may serve as an indicator of Bu GSH conjugating capacity of an individual. Objective To evaluate the utility of Bu MR to predict EFS in children undergoing allogeneic HSCT. Methods Two different cohorts with children receiving Bu in four times daily (QID, n=44) and once daily doses (QD, n=13) at St. Justine’s Hospital, Montreal were studied. Bu and Su levels were measured on day 3 of the conditioning regimen at the end of infusion (dose 9 in QID or dose 3 in QD dosing). EFS was defined from the time of transplant until death, relapse, or rejection, whichever occurred first. A receiver-operator characteristic curve (ROC) of Bu MRs was analyzed in relation to EFS. Cutoff values were defined based on the Youden´s J statistic. Results Twenty-two males and 22 females aged from 0.1 to 19.9 years (mean±SD: 7.2 ± 5.7) from Bu QID cohort had the mean MR of 5.9 (SD: 3.2). A cut off value of 4.9 in MR was chosen in ROC analysis in this cohort, with better sensitivity (71%) and specificity (70%) for EFS prediction (p=0.01, AUC= 0.7 (95% CI= 0.6–0.8). In QD cohort nine females, and four males aged between 0.4 and 15.8 years (6.7±5.1) had the mean MR of 29.3 (SD: 16.6). In ROC analysis, a cut off value of 25.06 was chosen with better sensitivity (100%) and specificity (100%) for EFS prediction (p=0.003; AUC=1.0). Conclusion The Bu MR on day 3 above 4.973 and 25.06 were associated with worse EFS in children undergoing HSCT and received Bu in QID and QD dosing schedules, respectively. Disclosure(s) Nothing to disclose

  • P97 Busulfan/sulfolane Metabolic Ratio on the third day of conditioning may predict the event-free survival in children receiving busulfan based conditioning prior to hematopoietic stem-cell transplantation
    Archives of Disease in Childhood, 2019
    Co-Authors: Crs Uppugunduri, M A Rezgui, Tiago Nava, Simona Jurkovic Mlakar, Yves Theoret, Henrique Bittencourt, Maja Krajinovic, Cp Huezo-diaz, Marc Ansari
    Abstract:

    Background Busulfan (Bu) is widely used as a component of myeloablative conditioning regimen before hematopoietic stem cell transplantation (HSCT) in children. Obtaining the Ratio of Bu to its metabolite sulfolane i.e. Metabolic Ratio (MR) may serve as an indicator of Bu GSH conjugating capacity of an individual. Objective To evaluate the utility of Bu MR to predict EFS in children undergoing allogeneic HSCT. Methods Two different cohorts with children receiving Bu in four times daily (QID, n=44) and once daily doses (QD, n=13) at St. Justine’s Hospital, Montreal were studied. Bu and Su levels were measured on day 3 of the conditioning regimen at the end of infusion (dose 9 in QID or dose 3 in QD dosing). EFS was defined from the time of transplant until death, relapse, or rejection, whichever occurred first. A receiver-operator characteristic curve (ROC) of Bu MRs was analyzed in relation to EFS. Cutoff values were defined based on the Youden´s J statistic. Results Twenty-two males and 22 females aged from 0.1 to 19.9 years (mean±SD: 7.2 ± 5.7) from Bu QID cohort had the mean MR of 5.9 (SD: 3.2). A cut off value of 4.9 in MR was chosen in ROC analysis in this cohort, with better sensitivity (71%) and specificity (70%) for EFS prediction (p=0.01, AUC= 0.7 (95% CI= 0.6–0.8). In QD cohort nine females, and four males aged between 0.4 and 15.8 years (6.7±5.1) had the mean MR of 29.3 (SD: 16.6). In ROC analysis, a cut off value of 25.06 was chosen with better sensitivity (100%) and specificity (100%) for EFS prediction (p=0.003; AUC=1.0). Conclusion The Bu MR on day 3 above 4.973 and 25.06 were associated with worse EFS in children undergoing HSCT and received Bu in QID and QD dosing schedules, respectively. Disclosure(s) Nothing to disclose