The effect of cimetidine or omeprazole on the pharmacokinetics of escitalopram in healthy subjects.
OBJECTIVE
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.
Malling
D
D
H. Lundbeck A/S, Valby, Denmark.
Poulsen
M N
MN
Søgaard
B
B
D000293:Adolescent; D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology*; D015283:Citalopram / Q000097:blood / Q000493:pharmacokinetics*; D003866:Depressive Disorder / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics*
D000897:Anti-Ulcer Agents; D002927:Cimetidine; D015283:Citalopram; D006635:Histamine H2 Antagonists; D009853:Omeprazole; D017367:Selective Serotonin Reuptake Inhibitors