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  • Title: Neuroendocrine response to intravenous citalopram in healthy control subjects: pharmacokinetic influences.
    Author: Lotrich FE, Bies R, Muldoon MF, Manuck SB, Smith GS, Pollock BG.
    Journal: Psychopharmacology (Berl); 2005 Mar; 178(2-3):268-75. PubMed ID: 15365685.
    Abstract:
    RATIONALE: The neuroendocrine response to intravenous citalopram may provide an acute, functional, in vivo measure of the neural serotonin (5-HT) system. OBJECTIVE: To refine the quantification of acute neuroendocrine responses following intravenous citalopram in studies of 5-HT function. METHODS: In 75 adult healthy subjects taking part in four similar protocols, we measured plasma prolactin and cortisol, as well as serial citalopram concentrations following intravenous citalopram (10 mg, 20 mg, 40 mg, 0.33 mg/kg) and placebo. The relationship between the AUC for intravenous citalopram during the first 150 min (AUC(150)) and the magnitude of the neuroendocrine response was determined. The role of pharmacokinetic (PK) parameters, as well as sensitivity to placebo injections, in influencing the neuroendocrine response to citalopram was then evaluated. RESULTS: Citalopram produced a dose-dependent increase in cortisol and prolactin. The maximal increase from baseline correlated significantly but modestly with citalopram's AUC(150) (prolactin r(2)=0.23, P<0.0001; cortisol r(2)=0.3, P<0.0001). Additionally, citalopram's AUC(150) was affected by between-subject differences in both the peripheral and central volume of distribution. However, the neuroendocrine responses to citalopram did not correlate with the responses to placebo. CONCLUSIONS: The parenteral citalopram challenge test is characterized by a modest concentration-response relationship, with concentration influenced by variable PK factors. Accounting for individual differences in drug distribution may improve the power of the citalopram challenge test, when used as an in vivo measure of central 5-HT function.
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