Article date: July 2010
By: Adriana Rocha, Eduardo B. Coelho, Stefânia A. Sampaio, Vera L. Lanchote, in Volume 70, Issue 1, pages 43-51
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
AIM
The study assessed the influence of omeprazole on the kinetic disposition of the (+)‐(S)‐citalopram (CITA) and (−)‐(R)‐CITA enantiomers in healthy volunteers.
METHODS
In a cross‐over study, healthy volunteers (n= 9) phenotyped as extensive metabolizers of CYP2C19 and CYP2D6 and with an oral midazolam clearance ranging from 10.9 to 149.3 ml min−1 kg−1 received a single dose of racemic CITA (20 mg orally) in combination or not with omeprazole (20 mg day−1 for 18 days). Serial blood samples were collected up to 240 h after CITA administration. CITA and demethylcitalopram (DCITA) enantiomers were analyzed by LC‐MS/MS using a Chiralcel® OD‐R column.
RESULTS
The kinetic disposition of CITA was enantioselective in the absence of treatment with omeprazole, with the observation of a greater proportion of plasma (−)‐(R)‐CITA [AUC S : R ratio of 0.53 (95% CI 0.41, 0.66) for CITA and 1.08 (95% CI 0.80, 1.76) for DCITA] than (+)‐(S)‐CITA. Racemic CITA administration to healthy volunteers in combination with omeprazole showed a loss of enantioselectivity in CITA pharmacokinetics with an increase of approximately 120% in plasma (+)‐(S)‐CITA concentrations [AUC S : R ratio of 0.95 (95% CI 0.72, 1.10) for CITA and 0.95 (95% CI 0.44, 1.72) for DCITA].
CONCLUSIONS
The administration of multiple doses of omeprazole preferentially inhibited (+)‐(S)‐CITA metabolism in healthy volunteers. Although omeprazole increased plasma concentrations of (+)‐(S)‐CITA by approximately 120%, it is difficult to evaluate the clinical outcome because the range of plasma CITA concentrations related to maximum efficacy and minimum risk of adverse effects has not been established.
DOI: 10.1111/j.1365-2125.2010.03649.x
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