Plasma Concentrations and Cardiovascular Effects of Citalopram Enantiomers After Oral Versus Infusion Citalopram Therapy in Dextromethorphan-Mephenytoin-Phenotyped Patients With Major Depression

Abstract

Background: Authors compared plasma concentrations of citalopram (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.Methods: Dextromethorphan-mephenytoin-phenotyped patients with depression were administered racemic CIT (days 1 and 2: 20 mg/d; days 3-10: 40 mg/d) 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 hours after drug administration, and on days 21 and 42. Plasma CIT and its metabolites were assayed by stereoselective high-performance liquid chromatography. Results: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: escitalopram (S-

Citalopram in vitro metabolism in a beagle dog: A role for CYP2D15 in the production of toxic didesmethylcitalopram?

“…Pharmacokinetic and pharmacogenetic studies in humans demonstrated the involvement of CYP2C19 and CYP2D6 in the N-demethylation of CIT to DCIT (Sindrup et al 1993;Herrlin et al 2003). CYP2C19 preferentially demethylates S-CIT rather than R-CIT (Herrlin et al 2003;Baumann et al 2021). Additional in vitro studies using human liver microsomes described the role of CYP3A4 in addition to CYP2C19 and CYP2D6 in this demethylation step (Kobayashi et al 1997;Rochat et al 1997;Olesen and Linnet 1999;von Moltke et al 1999;von Moltke et al 2001).…”