TY  - JOUR
AU  - Ingelman-Sundberg, Magnus
AU  - Jukić, Marin
AU  - Bråten, Line Skute
AU  - Kringen, Marianne Kristiansen
AU  - Molden, Espen
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5300
AB  - We   read   with   great   interest   the  paper  by  Zubiaur  et  al.1  on  the   analysis   of   a   genotype–phenotype  relationship  of  the  CYP2C:TG haplotype. This study, including 225 patients receiving one  of  6  different  drugs  and  liver  pieces  from  135  children  (median   age   7   years),   is   in   contrast to 2 studies by Bråten et al. using in vivo data from 875 escitalopram-treated2  and  840  sertraline-treated3    Norwegian    patients,  respectively,  in  which  significantly increased rate (+20 to 25%) of CYP2C19-dependent metabolism    of    these    drugs    was   found   for   the   CYP2C:TGhaplotype.
PB  - John Wiley and Sons Inc
T2  - Clinical Pharmacology and Therapeutics
T1  - What is the Current Clinical Impact of the CYP2CTG Haplotype?
VL  - 115
IS  - 2
SP  - 183
EP  - 183
DO  - 10.1002/cpt.3094
ER  - 

@article{
author = "Ingelman-Sundberg, Magnus and Jukić, Marin and Bråten, Line Skute and Kringen, Marianne Kristiansen and Molden, Espen",
year = "2024",
abstract = "We   read   with   great   interest   the  paper  by  Zubiaur  et  al.1  on  the   analysis   of   a   genotype–phenotype  relationship  of  the  CYP2C:TG haplotype. This study, including 225 patients receiving one  of  6  different  drugs  and  liver  pieces  from  135  children  (median   age   7   years),   is   in   contrast to 2 studies by Bråten et al. using in vivo data from 875 escitalopram-treated2  and  840  sertraline-treated3    Norwegian    patients,  respectively,  in  which  significantly increased rate (+20 to 25%) of CYP2C19-dependent metabolism    of    these    drugs    was   found   for   the   CYP2C:TGhaplotype.",
publisher = "John Wiley and Sons Inc",
journal = "Clinical Pharmacology and Therapeutics",
title = "What is the Current Clinical Impact of the CYP2CTG Haplotype?",
volume = "115",
number = "2",
pages = "183-183",
doi = "10.1002/cpt.3094"
}

Ingelman-Sundberg, M., Jukić, M., Bråten, L. S., Kringen, M. K.,& Molden, E.. (2024). What is the Current Clinical Impact of the CYP2CTG Haplotype?. in Clinical Pharmacology and Therapeutics
John Wiley and Sons Inc., 115(2), 183-183.
https://doi.org/10.1002/cpt.3094

Ingelman-Sundberg M, Jukić M, Bråten LS, Kringen MK, Molden E. What is the Current Clinical Impact of the CYP2CTG Haplotype?. in Clinical Pharmacology and Therapeutics. 2024;115(2):183-183.
doi:10.1002/cpt.3094 .

Ingelman-Sundberg, Magnus, Jukić, Marin, Bråten, Line Skute, Kringen, Marianne Kristiansen, Molden, Espen, "What is the Current Clinical Impact of the CYP2CTG Haplotype?" in Clinical Pharmacology and Therapeutics, 115, no. 2 (2024):183-183,
https://doi.org/10.1002/cpt.3094 . .

TY  - JOUR
AU  - Lenk, Hasan Çağın
AU  - Løvsletten Smith, Robert
AU  - O'Connell, Kevin
AU  - Jukić, Marin
AU  - Kringen, Marianne Kristiansen
AU  - Andreassen, Ole
AU  - Ingelman-Sundberg, Magnus
AU  - Molden, Espen
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4290
AB  - Clinical response of clozapine is closely associated with serum concentration. Although tobacco smoking is the key environmental factor underlying interindividual variability in clozapine metabolism, recent genome-wide studies suggest that CYP1A and NFIB genetic variants may also be of significant importance, but their quantitative impact is unclear. We investigated the effects of the rs2472297 C>T (CYP1A) and rs28379954 T>C (NFIB) polymorphisms on serum concentrations in smokers and nonsmokers. The study retrospectively included 526 patients with known smoking habits (63.7% smokers) from a therapeutic drug monitoring service in Norway. Clozapine dose-adjusted concentrations (C/D) and patient proportions with subtherapeutic levels (<1070 nmol/L) were compared between CYP1A/NFIB variant allele carriers and homozygous wild-type carriers (noncarriers), in both smokers and nonsmokers. Clozapine C/D was reduced in patients carrying CYP1A-T and NFIB-C variants versus noncarriers, both among smokers (−48%; p < 0.0001) and nonsmokers (−35%; p = 0.028). Patients who smoke carrying CYP1A-T and NFIB-C variants had a 66% reduction in clozapine C/D versus nonsmoking noncarriers (p < 0.0001). The patient proportion with subtherapeutic levels was 2.9-fold higher in patients who smoke carrying NFIB-C and CYP1A-T variants versus nonsmoking noncarriers (p < 0.0001). In conclusion, CYP1A and NFIB variants have significant and additive impact on clozapine dose requirements for reaching target serum concentrations. Patients who smoke carrying the studied CYP1A and NFIB variants, comprising 2.5% of the study population, may need threefold higher doses to prevent risk of clozapine undertreatment. The results suggest that pre-emptive genotyping of NFIB and CYP1A may be utilized to guide clozapine dosing and improve clinical outcomes in patients with treatment-resistant schizophrenia. © 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
PB  - John Wiley and Sons Inc
T2  - Clinical and Translational Science
T1  - Impact of NFIB and CYP1A variants on clozapine serum concentration—A retrospective naturalistic cohort study on 526 patients with known smoking habits
DO  - 10.1111/cts.13422
ER  - 

@article{
author = "Lenk, Hasan Çağın and Løvsletten Smith, Robert and O'Connell, Kevin and Jukić, Marin and Kringen, Marianne Kristiansen and Andreassen, Ole and Ingelman-Sundberg, Magnus and Molden, Espen",
year = "2022",
abstract = "Clinical response of clozapine is closely associated with serum concentration. Although tobacco smoking is the key environmental factor underlying interindividual variability in clozapine metabolism, recent genome-wide studies suggest that CYP1A and NFIB genetic variants may also be of significant importance, but their quantitative impact is unclear. We investigated the effects of the rs2472297 C>T (CYP1A) and rs28379954 T>C (NFIB) polymorphisms on serum concentrations in smokers and nonsmokers. The study retrospectively included 526 patients with known smoking habits (63.7% smokers) from a therapeutic drug monitoring service in Norway. Clozapine dose-adjusted concentrations (C/D) and patient proportions with subtherapeutic levels (<1070 nmol/L) were compared between CYP1A/NFIB variant allele carriers and homozygous wild-type carriers (noncarriers), in both smokers and nonsmokers. Clozapine C/D was reduced in patients carrying CYP1A-T and NFIB-C variants versus noncarriers, both among smokers (−48%; p < 0.0001) and nonsmokers (−35%; p = 0.028). Patients who smoke carrying CYP1A-T and NFIB-C variants had a 66% reduction in clozapine C/D versus nonsmoking noncarriers (p < 0.0001). The patient proportion with subtherapeutic levels was 2.9-fold higher in patients who smoke carrying NFIB-C and CYP1A-T variants versus nonsmoking noncarriers (p < 0.0001). In conclusion, CYP1A and NFIB variants have significant and additive impact on clozapine dose requirements for reaching target serum concentrations. Patients who smoke carrying the studied CYP1A and NFIB variants, comprising 2.5% of the study population, may need threefold higher doses to prevent risk of clozapine undertreatment. The results suggest that pre-emptive genotyping of NFIB and CYP1A may be utilized to guide clozapine dosing and improve clinical outcomes in patients with treatment-resistant schizophrenia. © 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.",
publisher = "John Wiley and Sons Inc",
journal = "Clinical and Translational Science",
title = "Impact of NFIB and CYP1A variants on clozapine serum concentration—A retrospective naturalistic cohort study on 526 patients with known smoking habits",
doi = "10.1111/cts.13422"
}

Lenk, H. Ç., Løvsletten Smith, R., O'Connell, K., Jukić, M., Kringen, M. K., Andreassen, O., Ingelman-Sundberg, M.,& Molden, E.. (2022). Impact of NFIB and CYP1A variants on clozapine serum concentration—A retrospective naturalistic cohort study on 526 patients with known smoking habits. in Clinical and Translational Science
John Wiley and Sons Inc..
https://doi.org/10.1111/cts.13422

Lenk HÇ, Løvsletten Smith R, O'Connell K, Jukić M, Kringen MK, Andreassen O, Ingelman-Sundberg M, Molden E. Impact of NFIB and CYP1A variants on clozapine serum concentration—A retrospective naturalistic cohort study on 526 patients with known smoking habits. in Clinical and Translational Science. 2022;.
doi:10.1111/cts.13422 .

Lenk, Hasan Çağın, Løvsletten Smith, Robert, O'Connell, Kevin, Jukić, Marin, Kringen, Marianne Kristiansen, Andreassen, Ole, Ingelman-Sundberg, Magnus, Molden, Espen, "Impact of NFIB and CYP1A variants on clozapine serum concentration—A retrospective naturalistic cohort study on 526 patients with known smoking habits" in Clinical and Translational Science (2022),
https://doi.org/10.1111/cts.13422 . .

TY  - JOUR
AU  - Bråten, Line Skute
AU  - Ingelman-Sundberg, Magnus
AU  - Jukić, Marin
AU  - Molden, Espen
AU  - Kringen, Marianne Kristiansen
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4181
AB  - Sertraline is a commonly used SSRI antidepressant drug, metabolized by CYP2C19 and CYP2B6, that exhibits a substantial interindividual variation in clinical response, of which only a part can be attributed to known genetic variants. In the current study we have examined the role of a newly discovered ultrarapid CYP2C:TG haplotype and CYP2B6 variants in order to identify the possible missing heritability for such variation in sertraline response in a large patient population (n = 840). Compared to the reference group (CYP2C19*1/*1, n = 160), sertraline exposure was increased by 128% in CYP2C19 PMs (n = 29, p < 0.001) and decreased by about 20% in CYP2C19 ultrarapid metabolizers (UMs) (homozygous carriers of CYP2C19*17 and/or CYP2C:TG haplotype) with the diplotypes CYP2C19*17/*17, CYP2C:TG/TG, or CYP2C19*17/CYP2C:TG (n = 135, p < 0.003, p = 0.022, p < 0.003, respectively). Interestingly, in patients carrying the increased function CYP2B6*4 allele, and also carrying the CYP2C19*17 and CYP2C:TG alleles (n = 10), sertraline exposure was 35.4% lower compared to the reference group, whereas in subjects being poor metabolizers (PM) in both the CYP2C19 and CYP2B6 gene, the sertraline concentrations were raised by 189%. In summary, the CYP2C19 variants including the CYP2C:TG haplotype had a significant impact on sertraline metabolism, as well as the CYP2B6*4, *6, and *9 alleles. Knowing the CYP2B6 and CYP2C19 genotype, including the CYP2C:TG haplotype status, can prospectively be useful to clinicians in making more appropriate sertraline dosing decisions.
PB  - John Wiley and Sons Inc
T2  - Clinical and Translational Science
T1  - Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population
VL  - 15
IS  - 9
SP  - 2135
EP  - 2145
DO  - 10.1111/cts.13347
ER  - 

@article{
author = "Bråten, Line Skute and Ingelman-Sundberg, Magnus and Jukić, Marin and Molden, Espen and Kringen, Marianne Kristiansen",
year = "2022",
abstract = "Sertraline is a commonly used SSRI antidepressant drug, metabolized by CYP2C19 and CYP2B6, that exhibits a substantial interindividual variation in clinical response, of which only a part can be attributed to known genetic variants. In the current study we have examined the role of a newly discovered ultrarapid CYP2C:TG haplotype and CYP2B6 variants in order to identify the possible missing heritability for such variation in sertraline response in a large patient population (n = 840). Compared to the reference group (CYP2C19*1/*1, n = 160), sertraline exposure was increased by 128% in CYP2C19 PMs (n = 29, p < 0.001) and decreased by about 20% in CYP2C19 ultrarapid metabolizers (UMs) (homozygous carriers of CYP2C19*17 and/or CYP2C:TG haplotype) with the diplotypes CYP2C19*17/*17, CYP2C:TG/TG, or CYP2C19*17/CYP2C:TG (n = 135, p < 0.003, p = 0.022, p < 0.003, respectively). Interestingly, in patients carrying the increased function CYP2B6*4 allele, and also carrying the CYP2C19*17 and CYP2C:TG alleles (n = 10), sertraline exposure was 35.4% lower compared to the reference group, whereas in subjects being poor metabolizers (PM) in both the CYP2C19 and CYP2B6 gene, the sertraline concentrations were raised by 189%. In summary, the CYP2C19 variants including the CYP2C:TG haplotype had a significant impact on sertraline metabolism, as well as the CYP2B6*4, *6, and *9 alleles. Knowing the CYP2B6 and CYP2C19 genotype, including the CYP2C:TG haplotype status, can prospectively be useful to clinicians in making more appropriate sertraline dosing decisions.",
publisher = "John Wiley and Sons Inc",
journal = "Clinical and Translational Science",
title = "Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population",
volume = "15",
number = "9",
pages = "2135-2145",
doi = "10.1111/cts.13347"
}

Bråten, L. S., Ingelman-Sundberg, M., Jukić, M., Molden, E.,& Kringen, M. K.. (2022). Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population. in Clinical and Translational Science
John Wiley and Sons Inc., 15(9), 2135-2145.
https://doi.org/10.1111/cts.13347

Bråten LS, Ingelman-Sundberg M, Jukić M, Molden E, Kringen MK. Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population. in Clinical and Translational Science. 2022;15(9):2135-2145.
doi:10.1111/cts.13347 .

Bråten, Line Skute, Ingelman-Sundberg, Magnus, Jukić, Marin, Molden, Espen, Kringen, Marianne Kristiansen, "Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population" in Clinical and Translational Science, 15, no. 9 (2022):2135-2145,
https://doi.org/10.1111/cts.13347 . .