Author
Listed:
- B Rochat
(Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Department of Education and Research, University of Lausanne, Lausanne, Switzerland)
- E Paus
(Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland, and Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland)
- C Maitre
(Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
PharmaciePlus Franches-Montagnes, Saignelégier, Switzerland)
- P Baumann
(Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland)
Abstract
After administration of the serotonergic antidepressant citalopram (CIT) to beagle dogs, they may experience severe convulsive attacks in relation with considerably higher plasma concentrations of the metabolite didesmethyl-CIT (DDCIT), when compared to those in humans medicated with CIT. This pilot study aimed at determining the role of cytochrome P-450 (CYP450) isozymes in the in vitro metabolism of CIT to desmethyl-CIT (DCIT), and of DCIT to DDCIT in the liver microsomes of a single beagle dog. The incubations with racemic CIT or DCIT reveal a high affinity enzyme with Km between 0.3 µM and 1.4 µM for S- and R-DCIT and S- and R-DDCIT productions, respectively. In comparison to human enzymes, the intrinsic clearance values of this high affinity enzyme are between 15 µL/(min x mg of protein) and 52 µL/(min x mg of protein), i.e. very high. In vitro experiments with inhibitors suggest that CYP2D15, which shows analogy with human CYP2D6, is by far the main CYP450 isozyme involved in the production of DCIT and DDCIT whereas CYP3A12 and CYP2C21/41 showed a weak implication. These observations partly explain why in humans, plasma concentrations of the toxic DDCIT are considerably lower than those observed in dogs, after administration of CIT.
Suggested Citation
B Rochat & E Paus & C Maitre & P Baumann, 2023.
"Citalopram in vitro metabolism in a beagle dog: A role for CYP2D15 in the production of toxic didesmethylcitalopram?,"
Veterinární medicína, Czech Academy of Agricultural Sciences, vol. 68(4), pages 135-144.
Handle:
RePEc:caa:jnlvet:v:68:y:2023:i:4:id:65-2022-vetmed
DOI: 10.17221/65/2022-VETMED
Download full text from publisher
As the access to this document is restricted, you may want to search for a different version of it.
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:caa:jnlvet:v:68:y:2023:i:4:id:65-2022-vetmed. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Ivo Andrle (email available below). General contact details of provider: https://www.cazv.cz/en/home/ .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.