Inhibition of human aromatase complex (CYP19) by antiepileptic drugs

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Standard

Inhibition of human aromatase complex (CYP19) by antiepileptic drugs. / Jacobsen, Naja Wessel; Halling-Sørensen, Bent; Birkved, Franziska Maria A Kramer.

In: Toxicology in Vitro, Vol. 22, No. 1, 2008, p. 146-153.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Jacobsen, NW, Halling-Sørensen, B & Birkved, FMAK 2008, 'Inhibition of human aromatase complex (CYP19) by antiepileptic drugs', Toxicology in Vitro, vol. 22, no. 1, pp. 146-153. https://doi.org/10.1016/j.tiv.2007.09.004

APA

Jacobsen, N. W., Halling-Sørensen, B., & Birkved, F. M. A. K. (2008). Inhibition of human aromatase complex (CYP19) by antiepileptic drugs. Toxicology in Vitro, 22(1), 146-153. https://doi.org/10.1016/j.tiv.2007.09.004

Vancouver

Jacobsen NW, Halling-Sørensen B, Birkved FMAK. Inhibition of human aromatase complex (CYP19) by antiepileptic drugs. Toxicology in Vitro. 2008;22(1):146-153. https://doi.org/10.1016/j.tiv.2007.09.004

Author

Jacobsen, Naja Wessel ; Halling-Sørensen, Bent ; Birkved, Franziska Maria A Kramer. / Inhibition of human aromatase complex (CYP19) by antiepileptic drugs. In: Toxicology in Vitro. 2008 ; Vol. 22, No. 1. pp. 146-153.

Bibtex

@article{f7e509f0c36811dcbee902004c4f4f50,
title = "Inhibition of human aromatase complex (CYP19) by antiepileptic drugs",
abstract = "Antiepileptic drugs and epilepsy are often associated with sexual disorder in women such as hyperandrogenism, menstrual disorders and ovarian cysts. In children, until puberty, a hormone imbalance may influence many aspects of development, e.g. growth and sexual maturation. The aromatase complex is the enzyme system that converts androgens to estrogens and consequently an inhibition may induce a hormone imbalance. Twelve antiepileptic drugs, used in mono or polytherapy for the treatment of children, were tested for their ability to inhibit aromatase (CYP19) with commercially available microsomes from transfected insect cells using dibenzylfluorescein as substrate. The drugs inhibiting CYP19 were: lamotrigine, oxcarbazepine, tiagabine, phenobarbital, phenytoin, ethosuximide, and valproate. The inhibitory effects (50{\%} reduction in activity compared to enzymes without inhibitor present) were in the range of 1.4-49.7 mM. Carbamazepine, gabapentin, primidone, topiramate and vigabatrin showed no inhibition. Additionally, binary drug combinations were tested to investigate if combination therapy could potentiate the aromatase inhibition. Additive inhibition was seen in combination experiments with valproate and phenobarbital. When adding carbamazepine to a range of valproate concentrations no additional inhibition was seen. The data for some of the AEDs show that side effects on steroid synthesis in humans due to inhibition of aromatase should be considered.",
keywords = "The Faculty of Pharmaceutical Sciences",
author = "Jacobsen, {Naja Wessel} and Bent Halling-S{\o}rensen and Birkved, {Franziska Maria A Kramer}",
year = "2008",
doi = "10.1016/j.tiv.2007.09.004",
language = "English",
volume = "22",
pages = "146--153",
journal = "Toxicology in Vitro",
issn = "0887-2333",
publisher = "Pergamon Press",
number = "1",

}

RIS

TY - JOUR

T1 - Inhibition of human aromatase complex (CYP19) by antiepileptic drugs

AU - Jacobsen, Naja Wessel

AU - Halling-Sørensen, Bent

AU - Birkved, Franziska Maria A Kramer

PY - 2008

Y1 - 2008

N2 - Antiepileptic drugs and epilepsy are often associated with sexual disorder in women such as hyperandrogenism, menstrual disorders and ovarian cysts. In children, until puberty, a hormone imbalance may influence many aspects of development, e.g. growth and sexual maturation. The aromatase complex is the enzyme system that converts androgens to estrogens and consequently an inhibition may induce a hormone imbalance. Twelve antiepileptic drugs, used in mono or polytherapy for the treatment of children, were tested for their ability to inhibit aromatase (CYP19) with commercially available microsomes from transfected insect cells using dibenzylfluorescein as substrate. The drugs inhibiting CYP19 were: lamotrigine, oxcarbazepine, tiagabine, phenobarbital, phenytoin, ethosuximide, and valproate. The inhibitory effects (50% reduction in activity compared to enzymes without inhibitor present) were in the range of 1.4-49.7 mM. Carbamazepine, gabapentin, primidone, topiramate and vigabatrin showed no inhibition. Additionally, binary drug combinations were tested to investigate if combination therapy could potentiate the aromatase inhibition. Additive inhibition was seen in combination experiments with valproate and phenobarbital. When adding carbamazepine to a range of valproate concentrations no additional inhibition was seen. The data for some of the AEDs show that side effects on steroid synthesis in humans due to inhibition of aromatase should be considered.

AB - Antiepileptic drugs and epilepsy are often associated with sexual disorder in women such as hyperandrogenism, menstrual disorders and ovarian cysts. In children, until puberty, a hormone imbalance may influence many aspects of development, e.g. growth and sexual maturation. The aromatase complex is the enzyme system that converts androgens to estrogens and consequently an inhibition may induce a hormone imbalance. Twelve antiepileptic drugs, used in mono or polytherapy for the treatment of children, were tested for their ability to inhibit aromatase (CYP19) with commercially available microsomes from transfected insect cells using dibenzylfluorescein as substrate. The drugs inhibiting CYP19 were: lamotrigine, oxcarbazepine, tiagabine, phenobarbital, phenytoin, ethosuximide, and valproate. The inhibitory effects (50% reduction in activity compared to enzymes without inhibitor present) were in the range of 1.4-49.7 mM. Carbamazepine, gabapentin, primidone, topiramate and vigabatrin showed no inhibition. Additionally, binary drug combinations were tested to investigate if combination therapy could potentiate the aromatase inhibition. Additive inhibition was seen in combination experiments with valproate and phenobarbital. When adding carbamazepine to a range of valproate concentrations no additional inhibition was seen. The data for some of the AEDs show that side effects on steroid synthesis in humans due to inhibition of aromatase should be considered.

KW - The Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.tiv.2007.09.004

DO - 10.1016/j.tiv.2007.09.004

M3 - Journal article

VL - 22

SP - 146

EP - 153

JO - Toxicology in Vitro

JF - Toxicology in Vitro

SN - 0887-2333

IS - 1

ER -

ID: 2306932