Influence of blood loss on the pharmacokinetics of citalopram.
Extended blood loss results in several compensatory physiological mechanisms, including transfer of extravascular fluid into the blood circulation. If drugs are present in the body, this fluid exchange may imply that blood drug concentrations found in a trauma victim may differ from the concentrations present at the time of the trauma. To address this issue, an animal model was used to investigate the influence of blood loss on pre-existing levels of the antidepressant drug citalopram and its demethylated metabolites. Rats were administered citalopram either acutely (40 mg/kg, orally) or chronically (20 mg/kg daily, subcutaneously) for 6 days using osmotic pumps. In the experimental rats, blood loss was accomplished by withdrawing 0.8 mL blood at 10 min intervals during 70 min. In the control rats, blood was withdrawn at 0 and 70 min only. Blood, brain and lung drug concentrations were analyzed with an enantioselective HPLC method. In the chronically treated rats, the ratios between final and initial citalopram concentrations were 1.08 +/- 0.15 and 1.01 +/- 0.09 in the experimental rats and controls, respectively, indicating no major effect of blood loss. In contrast, acute oral administration resulted in increased ratios in the exsanguinated rats as compared to controls (1.84 +/- 0.50 versus 0.73 +/- 0.07; p = 0.0495). In conclusion, the observation of increased blood drug levels in the acute oral rats indicates that absorption of fluid from the gastrointestinal tract may be important in the intravascular refill. Further, in the interpretation of post-mortem blood levels of drugs, these physiological mechanisms should be taken into account.
Kugelberg
Fredrik C
FC
Department of Forensic Medicine, Karolinska Institutet, Stockholm, Sweden. fredrik.kugelberg@ki.se
Alkass
Kanar
K
Kingbäck
Maria
M
Carlsson
Björn
B
Druid
Henrik
H
D000818:Animals; D001774:Blood Chemical Analysis; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D015283:Citalopram / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000032:analysis / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D005554:Forensic Medicine; D006470:Hemorrhage / Q000097:blood*; D008168:Lung / Q000737:chemistry; D023421:Models, Animal; D011180:Postmortem Changes; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D014947:Wounds and Injuries / Q000097:blood*
D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors; C514709:demethylcitalopram; C514710:didemethylcitalopram