In vivo steady-state pharmacokinetic outcome following clinical and toxic doses of racemic citalopram to rats

British Journal of Pharmacology
Fredrik C KugelbergFinn Bengtsson

Abstract

The thymoleptic drug citalopram (CIT) belongs to the selective serotonin reuptake inhibitors (SSRIs) and is today extensively used in psychiatry. Further clarification of the enantiomer-selective distribution of racemic CIT in both clinical and toxic doses is highly warranted. By a steady-state in vivo paradigm, rats underwent chronic systemic exposure for 10 days by using osmotic pumps and the total as well as the individual distributions of the S- and R-enantiomers of CIT, and its metabolites in serum and two different brain regions, were analysed. In serum, the S/R ratios in the groups treated with 10, 20, or 100 mg kg(-1) day(-1) were 0.94, 0.83, and 0.34, respectively. The ratios were almost the same in the brain regions. In the group treated with 100 mg kg(-1) day(-1), the serum and brain total CIT levels were found to be 20 times and 6 - 8 times higher than in the rats treated with 10 or 20 mg kg(-1) day(-1), respectively. In all groups, the CIT levels were higher in brain tissue as compared to serum. In a spontaneous open-field behavioural test, a correlation between clinical and toxic drug concentrations was observed. In conclusion, the R-enantiomer was present in an increased proportion compared with the S-enantiomer ...Continue Reading

References

Jan 1, 1992·Journal of Neural Transmission. General Section·J HyttelC Sánchez
Dec 1, 1988·British Journal of Clinical Pharmacology·A M EvansA A Somogyi
Jan 1, 1982·Progress in Neuro-psychopharmacology & Biological Psychiatry·K Fredricson Overø
Jan 1, 1982·Progress in Neuro-psychopharmacology & Biological Psychiatry·K Fredricson Overø
Dec 19, 1994·The American Journal of Medicine·J M Andrews, C B Nemeroff
Jan 1, 1995·Drug Metabolism Reviews·V Ravindranath, M R Boyd
Dec 1, 1995·Toxicology Letters·V RavindranathP S Tirumalai
Aug 3, 1996·Lancet·M OströmO Spigset
Nov 16, 1996·Lancet·F BrionM Durigon
Jan 1, 1997·Journal of Toxicology. Clinical Toxicology·M PersonneH Persson
May 31, 1997·Lancet·L GrundemarG Eklundh
Jul 1, 1998·International Journal of Legal Medicine·K WormB Kringsholm
Jan 11, 2000·Pharmacology & Toxicology·P DarcyP L Chambers
Mar 1, 2000·Brain Research·P VoirolP Baumann
Apr 25, 2000·Therapeutic Drug Monitoring·Z ZhengU Klotz

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Citations

Jul 4, 2003·Chirality·Fredrik C KugelbergFinn Bengtsson
Jul 14, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Dorota MaciagIan A Paul
Dec 21, 2004·Journal of Neurochemistry·Fenghua ChenOve Wiborg
Nov 18, 2008·Canadian Journal of Physiology and Pharmacology·Adriana RochaVera L Lanchote
Dec 25, 2012·Biological Psychiatry·Nesha S BurghardtJoseph E LeDoux
Jul 27, 2006·Basic & Clinical Pharmacology & Toxicology·Fredrik C KugelbergFinn Bengtsson
Sep 23, 2014·Current Biology : CB·Alexander SchaeferJulia Sacher
Jul 15, 2006·Forensic Science International : Synergy·Fredrik C KugelbergHenrik Druid
Nov 15, 2011·Brain Research·Sharonda S HarrisIan A Paul
Feb 23, 2013·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Louise KarlssonFredrik C Kugelberg
Sep 7, 2016·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Jenna L N SprowlesCharles V Vorhees
Jun 29, 2017·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Jenna L N SprowlesCharles V Vorhees
Dec 16, 2017·Journal of Analytical Toxicology·Michael NedahlKristian Linnet
May 20, 2004·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Toru KobayashiKazutaka Ikeda
Oct 31, 2002·Pharmacology & Toxicology·Fredrik C KugelbergFinn Bengtsson
Sep 26, 2003·Therapeutic Drug Monitoring·Yves Le Bloc'hPierre Baumann

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