AIMS: To investigate the effects of co-administration of cimetidine or omeprazole on the pharmacokinetics of escitalopram. METHODS: Two randomized placebo-controlled crossover studies were carried out. Sixteen healthy subjects were administered placebo, or cimetidine (400 mg twice daily) for 5 days (study 1) or omeprazole (30 mg once daily) for 6 days (study 2). On day 4 (study 1) or day 5 (study 2), a single dose of escitalopram (20 mg) was administered. Blood samples were taken at predetermined times for the measurement of serum concentrations of escitalopram and its demethylated metabolite (S-DCT). Treatment-emergent adverse events were also monitored. RESULTS: Co-administration with cimetidine caused a moderate increase in the systemic exposure [AUC0, infinity] to escitalopram (geometric mean ratio = 1.72, [95% CI 1.34, 2.21]) and a small increase in t(1/2) from 23.7 to 29.0 h (5.24 h [3.75, 6.70]). Co-administration with omeprazole also resulted in a moderate increase in the escitalopram AUC(0, infinity) (1.51 [1.39, 1.64]) and a small increase in t(1/2) from 26.5 to 34.8 h (8.3 h [6.44, 10.2]). There was no significant change in S-DCT AUC0, infinity after co-administration of either cimetidine or omeprazole. Co-administration of cimetidine or omeprazole had no effect on the incidence of treatment-emergent adverse events. CONCLUSIONS: In view of the good tolerability of escitalopram, the pharmacokinetic changes observed on co-administration with cimetidine or omeprazole are unlikely to be of clinical concern.
RCT Entities:
AIMS: To investigate the effects of co-administration of cimetidine or omeprazole on the pharmacokinetics of escitalopram. METHODS: Two randomized placebo-controlled crossover studies were carried out. Sixteen healthy subjects were administered placebo, or cimetidine (400 mg twice daily) for 5 days (study 1) or omeprazole (30 mg once daily) for 6 days (study 2). On day 4 (study 1) or day 5 (study 2), a single dose of escitalopram (20 mg) was administered. Blood samples were taken at predetermined times for the measurement of serum concentrations of escitalopram and its demethylated metabolite (S-DCT). Treatment-emergent adverse events were also monitored. RESULTS: Co-administration with cimetidine caused a moderate increase in the systemic exposure [AUC0, infinity] to escitalopram (geometric mean ratio = 1.72, [95% CI 1.34, 2.21]) and a small increase in t(1/2) from 23.7 to 29.0 h (5.24 h [3.75, 6.70]). Co-administration with omeprazole also resulted in a moderate increase in the escitalopram AUC(0, infinity) (1.51 [1.39, 1.64]) and a small increase in t(1/2) from 26.5 to 34.8 h (8.3 h [6.44, 10.2]). There was no significant change in S-DCT AUC0, infinity after co-administration of either cimetidine or omeprazole. Co-administration of cimetidine or omeprazole had no effect on the incidence of treatment-emergent adverse events. CONCLUSIONS: In view of the good tolerability of escitalopram, the pharmacokinetic changes observed on co-administration with cimetidine or omeprazole are unlikely to be of clinical concern.
Authors: L L von Moltke; D J Greenblatt; G M Giancarlo; B W Granda; J S Harmatz; R I Shader Journal: Drug Metab Dispos Date: 2001-08 Impact factor: 3.922
Authors: N Klein; J Sacher; T Geiss-Granadia; T Attarbaschi; N Mossaheb; R Lanzenberger; C Pötzi; A Holik; C Spindelegger; S Asenbaum; R Dudczak; J Tauscher; S Kasper Journal: Psychopharmacology (Berl) Date: 2006-09-06 Impact factor: 4.530