title: EEG profile of litoxetine after single and repeated administration in healthy volunteers.
abstract: 1. Litoxetine is a selective serotonin reuptake inhibitor with antidepressant activity in animal models and in depressed patients. 2. This double-blind, cross-over, placebo-controlled study was carried out in 12 healthy young male volunteers. The aim was to assess the EEG profile of litoxetine in parallel with its pharmacokinetics after a single dose or multiple administrations for 4 days (6 doses) of two dosages (10 mg and 25 mg). Spectral analysis of four EEG leads (F4-T4, F3-T3, T4-02 and T3-01) was done up to 12 h post-dose. 3. In single or multiple doses, litoxetine induced EEG changes characterised by a dose-related increase in fast beta energies, mainly beta 2, without any changes in slow waves (delta and theta). A slight reduction in alpha activity occurred only after repeated doses. 4. EEG changes occurred after a single oral administration and lasted at least 12 h with litoxetine blood concentrations ranging from 4 to 10 ng ml-1. With repeated administrations, the pharmacodynamic steady-state was achieved as the increase in beta 2 energies was the same before and 12 h post-dose. These effects occurred with litoxetine blood concentrations ranging from 3 to 7 ng ml-1 with the 10 mg dosage and from 8 to 18 ng ml-1 with the 25 mg dosage. The EEG profile did not change after 4 days of repeated administration, indicating that tolerance did not develop. 5. Cmax and AUC showed proportionality between the administered dosages of 10 and 25 mg.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Synthélabo Recherche (L.E.R.S.), Bagneux, France.
authors.forename: A
authors.initials: A
authors.lastname: Patat
authors.forename: S
authors.initials: S
authors.lastname: Trocherie
authors.forename: J J
authors.initials: JJ
authors.lastname: Thébault
authors.forename: P
authors.initials: P
authors.lastname: Rosenzweig
authors.forename: C
authors.initials: C
authors.lastname: Dubruc
authors.forename: G
authors.initials: G
authors.lastname: Bianchetti
authors.forename: P L
authors.initials: PL
authors.lastname: Morselli
authors.forename: L A
authors.initials: LA
authors.lastname: Court
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D006801:Humans; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D010880:Piperidines; D017367:Selective Serotonin Reuptake Inhibitors; C057048:litoxetine