Serum concentrations of citalopram--dose-dependent variation in R- and S-enantiomer ratios.
BACKGROUND
The antidepressive effect of racemic citalopram (CIT) is exerted by S-CIT, while R-CIT is a partial antagonist to S-CIT. Since R-and S-CIT are metabolized by different pathways, we investigated whether the ratio of S- and R-CIT may differ between individuals on the same dose of racemic CIT, and if a possible variability in the R/S-ratio could be dose-dependent.


METHODS
A chiral analysis of R- and S-CIT in serum samples taken from 88 female patients receiving treatment with racemic CIT was performed using high-pressure liquid chromatography.


RESULTS
The mean levels of R-CIT were significantly higher than those of S-CIT in all dose groups. The R/S-CIT ratio increased from 1.99 to 2.45 with an increase in the dose (p<0.05), and the interindividual variance in the R/S-CIT ratio was up to four-fold on the same dosage.


CONCLUSIONS
Our findings show that the stereoselective metabolism of citalopram IN VIVO has pharmacokinetic consequences reflected by dose dependent variations of enantiomeric drug concentrations, as well as substantial interindividual variabilities in the ratios of the concentrations. The clinical consequences, however, are unclear and should be further explored.
Tanum
L
L
Department of Research & Education in Psychiatry, Diakonhjemmet Hospital, Oslo, Norway. lars.tanum@medisin.uio.no
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry*; D015283:Citalopram / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry; D013237:Stereoisomerism; D055815:Young Adult
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors