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

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Harvard

Stage, C, Jürgens, G, Guski, LS, Thomsen, R, Bjerre, D, Ferrero-Miliani, L, Lyauk, YK, Rasmussen, HB, Dalhoff, K, INDICES Consortium (for members of this consortium-see Supplementum) & INDICES consortium 2017, 'The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers', Basic & clinical pharmacology & toxicology. 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., Rasmussen, H. B., Dalhoff, K., INDICES Consortium (for members of this consortium-see Supplementum), & INDICES consortium (2017). The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers. Basic & clinical pharmacology & toxicology. https://doi.org/10.1111/bcpt.12835

CBE

MLA

Vancouver

Author

Stage, Claus ; Jürgens, Gesche ; Guski, Louise Schow ; Thomsen, Ragnar ; Bjerre, Ditte ; Ferrero-Miliani, Laura ; Lyauk, Yassine Kamal ; Rasmussen, Henrik Berg ; Dalhoff, Kim ; INDICES Consortium (for members of this consortium-see Supplementum) ; INDICES consortium. / The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers. In: Basic & clinical pharmacology & toxicology. 2017.

Bibtex

@article{ae98a91729314cf39c636bab170a132c,
title = "The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers",
abstract = "This 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 (control group, 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 ng/ml x h in the control group versus 310, 282, 294, 344 and 306 ng/ml x h in groups 2-6, respectively). The terminal half-life of enalaprilat was significantly longer in group 6 compared with 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.",
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 Rasmussen, {Henrik Berg} and Kim Dalhoff and {INDICES Consortium (for members of this consortium-see Supplementum)} and {INDICES consortium} and Pia Jeppesen and Pagsberg, {Anne Katrine} and Plessen, {Kerstin J} and Kristine Kaalund-Brok and Tine Houmann",
note = "{\textcopyright} 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).",
year = "2017",
month = jul,
doi = "10.1111/bcpt.12835",
language = "English",
journal = "Basic & Clinical Pharmacology & Toxicology Online",
issn = "1742-7843",
publisher = "Wiley-Blackwell Publishing Ltd",

}

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 - Rasmussen, Henrik Berg

AU - Dalhoff, Kim

AU - INDICES Consortium (for members of this consortium-see Supplementum)

AU - INDICES consortium

A2 - Jeppesen, Pia

A2 - Pagsberg, Anne Katrine

A2 - Plessen , Kerstin J

A2 - Kaalund-Brok, Kristine

A2 - Houmann, Tine

N1 - © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

PY - 2017/7

Y1 - 2017/7

N2 - This 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 (control group, 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 ng/ml x h in the control group versus 310, 282, 294, 344 and 306 ng/ml x h in groups 2-6, respectively). The terminal half-life of enalaprilat was significantly longer in group 6 compared with 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.

AB - This 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 (control group, 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 ng/ml x h in the control group versus 310, 282, 294, 344 and 306 ng/ml x h in groups 2-6, respectively). The terminal half-life of enalaprilat was significantly longer in group 6 compared with 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.

KW - Journal Article

U2 - 10.1111/bcpt.12835

DO - 10.1111/bcpt.12835

M3 - Journal article

C2 - 28639420

JO - Basic & Clinical Pharmacology & Toxicology Online

JF - Basic & Clinical Pharmacology & Toxicology Online

SN - 1742-7843

ER -

ID: 51521057