The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers

Research output: Contribution to journal › Journal article › Research › peer-review

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The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers. / Stage, Claus; Jürgens, Gesche; Guski, Louise Schow; Thomsen, Ragnar; Bjerre, Ditte; Ferrero-Miliani, Laura; Lyauk, Yassine Kamal; Berg Rasmussen, Henrik; Dalhoff, Kim; INDICES Consortium.

In: Basic & Clinical Pharmacology & Toxicology, Vol. 121, No. 6, 06.12.2017, p. 487–492.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Stage, C, Jürgens, G, Guski, LS, Thomsen, R, Bjerre, D, Ferrero-Miliani, L, Lyauk, YK, Berg Rasmussen, H, Dalhoff, K & INDICES Consortium 2017, 'The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers', Basic & Clinical Pharmacology & Toxicology, vol. 121, no. 6, pp. 487–492. https://doi.org/10.1111/bcpt.12835

APA

Stage, C., Jürgens, G., Guski, L. S., Thomsen, R., Bjerre, D., Ferrero-Miliani, L., Lyauk, Y. K., Berg Rasmussen, H., Dalhoff, K., & INDICES Consortium (2017). The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers. Basic & Clinical Pharmacology & Toxicology, 121(6), 487–492. https://doi.org/10.1111/bcpt.12835

Vancouver

Stage C, Jürgens G, Guski LS, Thomsen R, Bjerre D, Ferrero-Miliani L et al. The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers. Basic & Clinical Pharmacology & Toxicology. 2017 Dec 6;121(6):487–492. https://doi.org/10.1111/bcpt.12835

Author

Stage, Claus ; Jürgens, Gesche ; Guski, Louise Schow ; Thomsen, Ragnar ; Bjerre, Ditte ; Ferrero-Miliani, Laura ; Lyauk, Yassine Kamal ; Berg Rasmussen, Henrik ; Dalhoff, Kim ; INDICES Consortium. / The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers. In: Basic & Clinical Pharmacology & Toxicology. 2017 ; Vol. 121, No. 6. pp. 487–492.

Bibtex

@article{cf5668506be54d4da56959b17528458b,

title = "The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers",

abstract = "The present study investigated the influence of variations in the carboxylesterase 1 gene (CES1) on the pharmacokinetics of enalapril. Forty-three healthy, Danish, Caucasian volunteers representing different pre-defined genotypes each received 10 mg of enalapril. At specified time points, plasma concentrations of enalapril and the active metabolite enalaprilat were measured. The volunteers were divided into six different groups according to their genetic profile of CES1: Group 1 (controls, n=16) with two CES1 copies without non-synonymous SNPs in the exons; group 2 (n=5) with four copies of CES1; group 3 (n=6) harbouring the G143E polymorphism; group 4 (n=2) with three CES1 copies and increased transcriptional activity of the duplication (CES1A2); group 5 (n=4) harbouring the CES1A1c variant; and group 6 (n=10) with three CES1 copies and the common promoter with low transcriptional activity of the duplication. The median AUC of enalaprilat in the control group was not significantly different from any of the other five groups (297 μg/l x h in the control group versus 310, 282, 294, 344 and 306 μg/l x h in group 2-6, respectively). The terminal half-life of enalaprilat was significantly longer in group 6 compared to the control group (26.7 hr versus 12.7 hr, respectively). However, this was not considered clinically relevant. In conclusion, none of the selected variations of CES1 had a clinically relevant impact on the metabolism of enalapril. This article is protected by copyright. All rights reserved.",

keywords = "Journal Article",

author = "Claus Stage and Gesche J{\"u}rgens and Guski, {Louise Schow} and Ragnar Thomsen and Ditte Bjerre and Laura Ferrero-Miliani and Lyauk, {Yassine Kamal} and {Berg Rasmussen}, Henrik and Kim Dalhoff and {INDICES Consortium}",

year = "2017",

month = dec,

day = "6",

doi = "10.1111/bcpt.12835",

language = "English",

volume = "121",

pages = "487–492",

journal = "Basic and Clinical Pharmacology and Toxicology",

issn = "1742-7835",

publisher = "Wiley-Blackwell",

number = "6",

}

RIS

TY - JOUR

T1 - The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers

AU - Stage, Claus

AU - Jürgens, Gesche

AU - Guski, Louise Schow

AU - Thomsen, Ragnar

AU - Bjerre, Ditte

AU - Ferrero-Miliani, Laura

AU - Lyauk, Yassine Kamal

AU - Berg Rasmussen, Henrik

AU - Dalhoff, Kim

AU - INDICES Consortium

PY - 2017/12/6

Y1 - 2017/12/6

N2 - The present study investigated the influence of variations in the carboxylesterase 1 gene (CES1) on the pharmacokinetics of enalapril. Forty-three healthy, Danish, Caucasian volunteers representing different pre-defined genotypes each received 10 mg of enalapril. At specified time points, plasma concentrations of enalapril and the active metabolite enalaprilat were measured. The volunteers were divided into six different groups according to their genetic profile of CES1: Group 1 (controls, n=16) with two CES1 copies without non-synonymous SNPs in the exons; group 2 (n=5) with four copies of CES1; group 3 (n=6) harbouring the G143E polymorphism; group 4 (n=2) with three CES1 copies and increased transcriptional activity of the duplication (CES1A2); group 5 (n=4) harbouring the CES1A1c variant; and group 6 (n=10) with three CES1 copies and the common promoter with low transcriptional activity of the duplication. The median AUC of enalaprilat in the control group was not significantly different from any of the other five groups (297 μg/l x h in the control group versus 310, 282, 294, 344 and 306 μg/l x h in group 2-6, respectively). The terminal half-life of enalaprilat was significantly longer in group 6 compared to the control group (26.7 hr versus 12.7 hr, respectively). However, this was not considered clinically relevant. In conclusion, none of the selected variations of CES1 had a clinically relevant impact on the metabolism of enalapril. This article is protected by copyright. All rights reserved.

AB - The present study investigated the influence of variations in the carboxylesterase 1 gene (CES1) on the pharmacokinetics of enalapril. Forty-three healthy, Danish, Caucasian volunteers representing different pre-defined genotypes each received 10 mg of enalapril. At specified time points, plasma concentrations of enalapril and the active metabolite enalaprilat were measured. The volunteers were divided into six different groups according to their genetic profile of CES1: Group 1 (controls, n=16) with two CES1 copies without non-synonymous SNPs in the exons; group 2 (n=5) with four copies of CES1; group 3 (n=6) harbouring the G143E polymorphism; group 4 (n=2) with three CES1 copies and increased transcriptional activity of the duplication (CES1A2); group 5 (n=4) harbouring the CES1A1c variant; and group 6 (n=10) with three CES1 copies and the common promoter with low transcriptional activity of the duplication. The median AUC of enalaprilat in the control group was not significantly different from any of the other five groups (297 μg/l x h in the control group versus 310, 282, 294, 344 and 306 μg/l x h in group 2-6, respectively). The terminal half-life of enalaprilat was significantly longer in group 6 compared to the control group (26.7 hr versus 12.7 hr, respectively). However, this was not considered clinically relevant. In conclusion, none of the selected variations of CES1 had a clinically relevant impact on the metabolism of enalapril. This article is protected by copyright. All rights reserved.

KW - Journal Article

U2 - 10.1111/bcpt.12835

DO - 10.1111/bcpt.12835

M3 - Journal article

C2 - 28639420

VL - 121

SP - 487

EP - 492

JO - Basic and Clinical Pharmacology and Toxicology

JF - Basic and Clinical Pharmacology and Toxicology

SN - 1742-7835

IS - 6

ER -

ID: 180401806