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The effect of cimetidine or omeprazole on the pharmacokinetics of escitalopram in healthy subjects
Author(s) -
Malling D.,
Poulsen M. N.,
Søgaard B.
Publication year - 2005
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2005.02423.x
Subject(s) - escitalopram , omeprazole , cimetidine , pharmacokinetics , placebo , crossover study , medicine , pharmacology , tolerability , oral administration , adverse effect , cmax , alternative medicine , pathology , hippocampus , antidepressant
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 t ½ 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 t ½ 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.