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  • Title: Plasma levels of citalopram enantiomers and metabolites in elderly patients.
    Author: Foglia JP, Pollock BG, Kirshner MA, Rosen J, Sweet R, Mulsant B.
    Journal: Psychopharmacol Bull; 1997; 33(1):109-12. PubMed ID: 9133760.
    Abstract:
    Ten patients with dementia and significant behavioral disturbances (mean age of 77.2 +/- 8.2 years) received citalopram, 10 mg/day for 3 days, followed by 20 mg/day for 2 weeks. Six of the 10 patients completing 17 days of treatment had a clinically impressive response, as assessed by significant improvement in six target items on the Neurobehavioral Rating Scale. Eight patients were also analyzed by measuring the racemic and enantiomeric plasma levels of citalopram (CIT) and desmethylcitalopram (DCIT). A sensitive high-performance liquid chromatography (HPLC) assay for citalopram enantiomers and metabolites was developed using ultraviolet detection. The lower limit of detection was 10 ng/ml for each enantiomer. Steady-state plasma level ranges were 11.2 to 92.2 ng/ml for the biologically active S(+) citalopram and 12.8 to 95.7 ng/ml for the inactive R(-) enantiomer. For the S and R enantiomers of desmethylcitalopram, plasma levels ranged from 11.0 to 22.0 ng/ml and 9.2 to 22.0 ng/ml, respectively. The racemic citalopram plasma level to dose ratio of 3.50 was higher than the ratio (1.96) reported by Overo (1982) for 55 younger patients. The stereoselective metabolism of the enantiomers for citalopram and desmethylcitalopram (S(+) and R(-) enantiomers) in these older subjects differed from that reported in younger patients, suggesting possible age-associated changes in CYP2C19 activities. We hypothesize that quantification of S(+) citalopram will permit a more accurate examination of dose/response relationships. This measure seems to be especially important for older subjects, given the wide ranges and higher concentrations evident from our preliminary results.
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