The effect of cimetidine or omeprazole on the pharmacokinetics of escitalopram in healthy subjects

• Published in: British journal of clinical pharmacology 2005-09, Vol.60 (3), p.287-290
• Main Authors: Malling, D., Poulsen, M. N., Søgaard, B.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anti-Ulcer Agents - administration & dosage; Anti-Ulcer Agents - pharmacology; Biological and medical sciences; Cimetidine - administration & dosage; Cimetidine - pharmacology; Citalopram - blood; Citalopram - pharmacokinetics; CYP2C19; CYP2D6; Depressive Disorder - drug therapy; Drug Interactions; Drug Therapy, Combination; enantiomers; escitalopram; Female; Histamine H2 Antagonists - administration & dosage; Histamine H2 Antagonists - pharmacology; Humans; Male; Medical sciences; metabolism; Middle Aged; Omeprazole - administration & dosage; Omeprazole - pharmacology; Pharmacology. Drug treatments; Serotonin Uptake Inhibitors - blood; Serotonin Uptake Inhibitors - pharmacokinetics
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/j.1365-2125.2005.02423.x

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 [AUC(0, ∞)] to escitalopram (geometric mean ratio = 1.72, [95% CI 1.34, 2.21]) and a small increase in t½ 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, ∞) (1.51 [1.39, 1.64]) and a small increase in t½ from 26.5 to 34.8 h (8.3 h [6.44, 10.2]). There was no significant change in S‐DCT AUC(0, ∞) 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.