Therapeutic Drug Monitoring of Paroxetine in a Naturalistic Clinical Setting

Paroxetine (PXT) is an antidepressant drug first introduced in Sweden in 1991. It is a selective serotonin reuptake inhibitor (SSRI) and during the year 1992–1999, the time for the data collection for this study, the mean DDD/TIND (defined daily dose/thousand inhabitants) in Sweden was 3.16 (±1.17).

We here present paroxetine pharmacokinetics derived from routine therapeutic drug monitoring (TDM) data. A total of 2396 analyses were performed, with high-performance liquid chromatographic method with ultraviolet detection, as part of a clinical routine. Due to lack of vital information 614 samples were excluded. The remaining, 1782, was further analysed. Predefined extensive exclusion criteria (sample must be taken as a trough value in steady state, PXT must be detectable, no interaction with other drugs or intoxication was allowed) resulted in that another 46% of the request forms were excluded. The 563 samples, that were further scrutinized, were all drawn as trough values (15–30 hours), in steady state, with detectable PXT concentrations and only the first sample per patient was included for inter-individual PK-variance for PXT in ss. There were 50 patients who had more than one sample that fulfilled the criteria and this group was further analysed with focus on intra-individual variability.

A great interindividual variability in patients on the same dose, as seen before, was observed. In the group on a 20mg dose, n=215, CV% was 141%. For the whole group, mean dose 32mg, n=563, CV% was 101%. A factor that was observed was that smokers had a tendency towards lower concentrations of PXT despite higher administered doses.