Distribution of citalopram enantiomers following medication with racemic citalopram - a naturalistic therapeutic drug monitoring study

PURPOSE: There are very few reports describing to which extent sex, age, dose and time from dose intake affect the enantiomeric distribution during treatment with citalopram. The aim of the present study was to quantify the impact of these factors on the active S-enantiomer during treatment with citalopram. METHODS: Samples analysed for citalopram in a routine therapeutic drug monitoring setting were included. The analytical method consisted of enantiomeric separation and quantification of R- and S-citalopram. We employed a linear mixed model to account for multiple samples from the same patient. RESULTS: A total of 305 samples was included. The mean (± SD) proportion of S-citalopram in the total sample was 34.2 ± 8.1%, corresponding to a mean S/R ratio of 0.52 ± 0.17. According to the linear mixed model, the proportion of S-citalopram increased with 0.69 percentage points per decade of age. Increasing the time interval from dose intake to sampling reduced this proportion with 1.10 percentage points every 6 h. For example, if the sample was obtained 24 h after intake in a person aged 40, the proportion of S-citalopram was 32.7%; while if the sample was obtained 12 h after intake the proportion was 34.9%. Sex and dose did not impact significantly. CONCLUSION: The percentage of S-citalopram in plasma during treatment with citalopram increased with patient age and decreased with the time from dose intake. In contrast, sex and dose did not significantly affect the percentage of S-citalopram.