The main objectives of this study were to outline the inter- and intraindividual and overall pharmacokinetic variability of S-citalopram, S-desmethylcitalopram, and S-didesmethylcitalopram in serum by means of therapeutic drug monitoring; and to investigate potential correlations between the serum concentration and simultaneously collected clinical data. The study was conducted on outpatients in Sweden in 2002 to 2005. Included in the pharmacokinetic evaluation were 155 patients (68% women and 32% men) aged 17 to 95 years (average, 51 years). One serum sample per patient, taken as a trough value in steady state, was assessed. For the inter- and intraindividual variation calculation, 16 patients were included with two eligible samples each. The median daily dose was 20 mg/day (range, 5-40 mg). Extensive overall serum concentration variability was seen for all dose levels. The interindividual coefficient of variation for dose-normalized concentrations was 71% for S-citalopram, 36% for S-desmethylcitalopram, and 50% for S-didesmethylcitalopram. The intraindividual variations over time for the same parameters were approximately 30%, except for the ratio S-desmethylcitalopram/S-citalopram, which was 23%. The median S-desmethylcitalopram level was approximately 60% of the parent substance and the S-didesmethylcitalopram level approximately 9%. Higher age was correlated with higher serum concentrations, but no gender-related concentration differences were found. A majority (76%) of the patients took one or more drugs in addition to escitalopram, but concomitant medication did not seem to interact with escitalopram. However, women taking oral contraceptives showed a lower metabolic ratio compared with age-matched women. As a result of the wide range of the ratio in this population, these findings are not considered of clinical relevance.
From the *Department of Clinical Pharmacology, Faculty of Health Sciences, Linköping University Hospital, Linköping, Sweden; †Medical head of project, Head of Task Force; and ‡Owe Bodlund (Umeå), Claes-Göran Eckerström (Mölndal), Thomas Eriksson (Linköping), Ingemar Sjödin (Linköping), and Jan Steijner (Mölndal).
Received for publication January 27, 2007; accepted August 31, 2007.
Financial support for this study provided by H. Lundbeck AB, Sweden, through an agreement made with Berzelius Clinical Research Center (BCRC). In turn, BCRC provided the Task Force for TDM of escitalopram in Sweden with an unrestricted commission to undertake this study. Thus, neither of the companies was responsible for creation of the study protocol, the data analysis, data interpretation, or writing of the manuscript. Salaries financing participating researchers, and not supported by grants from BCRC, were in part generously supported by regional funds for clinical research (ALF) by the County Council of Östergötland, Sweden, and by continuing grants from the Swedish Research Council (2006-4345; Finn Bengtsson).
Correspondence: Margareta Reis, PhD, Institute of Laboratory Medicine, Department of Clinical and Experimental Pharmacology, Lund University Hospital, 221 85 Lund, Sweden (e-mail: firstname.lastname@example.org).