Plasma Concentrations and Cardiovascular Effects of Citalopram Enantiomers after Oral vs. Infusion Citalopram Therapy in Dextromethorphan- and Mephenytoin-Phenotyped Patients with Major Depression.

Details

Serval ID
serval:BIB_8E9409E4FB71
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Plasma Concentrations and Cardiovascular Effects of Citalopram Enantiomers after Oral vs. Infusion Citalopram Therapy in Dextromethorphan- and Mephenytoin-Phenotyped Patients with Major Depression.
Journal
Therapeutic drug monitoring
Author(s)
Baumann Pierre, Bertschy Gilles, Ramseier Fritz, Nil Rico
ISSN
1536-3694 (Electronic)
ISSN-L
0163-4356
Publication state
Published
Issued date
21/09/2020
Peer-reviewed
Oui
Volume
43
Number
3
Pages
436-442
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Authors compared plasma concentrations of CIT enantiomers and their metabolites in patients with depression administered either intravenously (IV) or as oral racemic CIT. Then, plasma concentrations were related to the metabolism of probes used for phenotyping patients with depression for CYP2C19 and CYP2D6 activity and cardiovascular functions.
Dextromethorphan-mephenytoin-phenotyped patients with depression were administered racemic CIT (days 1 and 2: 20 mg/day; days 3-10: 40 mg/day) either orally or as a slow-drop infusion for 10 days and were then orally administered the drug for another 32 days. Blood probes were collected at the time of minimal and maximal concentrations on day 10, immediately before and 2 h after drug administration, and on days 21 and 42. Plasma CIT and its metabolites were assayed by stereo-selective HPLC.
The following concentrations (ng/mL) were noted in the group receiving active IV infusion (IV-POS group, n = 27) of racemic CIT on day 10, before drug administration: S-CIT: 24±10.2; R-CIT: 45±14.5; S-desmethyl-CIT: 13±4.4; R-desmethyl-CIT: 17±8.2. In patients receiving oral administration (POS-POS group, n = 25), the values were 30±12.7, 51±17.4, 13±4.6, and 17±7.9 ng/mL, respectively. In the IV-POS group, three patients were poor dextromethorphan (CYP2D6) metabolizers; in the POS-POS group, one was a poor mephenytoin (CYP2C19) metabolizer. On day 10, before CIT treatment, S/R-CIT and S/R-mephenytoin ratios were significantly correlated, determined at baseline. Overall, CIT reduced heart rate but did not significantly modify QTc. No relationship was found between any cardiovascular parameters and pharmacokinetic and pharmacogenetic data.
Owing to CLT's high bioavailability, the plasma concentrations of its enantiomers remained largely independent on the administration route. CYP2C19 preferentially demethylated S-CIT after CIT therapy.
Keywords
depressive patients, citalopram, infusion, pharmacokinetics, enantiomers, pharmacogenetics, CYP2C19, CYP2D6, QTc
Pubmed
Create date
31/10/2020 14:47
Last modification date
23/05/2021 6:38
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