Neuroendocrine response to intravenous citalopram in healthy control subjects

Pharmacokinetic influences

Francis E. Lotrich, Robert Bies, Matthew F. Muldoon, Stephen B. Manuck, Gwenn S. Smith, Bruce G. Pollock

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 (AUC150) 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 AUC150 (prolactin r 2=0.23, P2=0.3, P150 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.

Original languageEnglish (US)
Pages (from-to)268-275
Number of pages8
JournalPsychopharmacology
Volume178
Issue number2-3
DOIs
StatePublished - Mar 2005
Externally publishedYes

Fingerprint

Citalopram
Healthy Volunteers
Pharmacokinetics
Serotonin
Prolactin
Placebos
Hydrocortisone
Individuality
Area Under Curve

Keywords

  • Citalopram
  • Cortisol
  • Neuroendocrine challenge
  • Pharmacokinetic
  • Prolactin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Neuroendocrine response to intravenous citalopram in healthy control subjects : Pharmacokinetic influences. / Lotrich, Francis E.; Bies, Robert; Muldoon, Matthew F.; Manuck, Stephen B.; Smith, Gwenn S.; Pollock, Bruce G.

In: Psychopharmacology, Vol. 178, No. 2-3, 03.2005, p. 268-275.

Research output: Contribution to journalArticle

Lotrich, Francis E. ; Bies, Robert ; Muldoon, Matthew F. ; Manuck, Stephen B. ; Smith, Gwenn S. ; Pollock, Bruce G. / Neuroendocrine response to intravenous citalopram in healthy control subjects : Pharmacokinetic influences. In: Psychopharmacology. 2005 ; Vol. 178, No. 2-3. pp. 268-275.
@article{1ddf016807f248e5ab6dd3779b30d8bc,
title = "Neuroendocrine response to intravenous citalopram in healthy control subjects: Pharmacokinetic influences",
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 (AUC150) 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 AUC150 (prolactin r 2=0.23, P2=0.3, P150 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.",
keywords = "Citalopram, Cortisol, Neuroendocrine challenge, Pharmacokinetic, Prolactin",
author = "Lotrich, {Francis E.} and Robert Bies and Muldoon, {Matthew F.} and Manuck, {Stephen B.} and Smith, {Gwenn S.} and Pollock, {Bruce G.}",
year = "2005",
month = "3",
doi = "10.1007/s00213-004-2006-4",
language = "English (US)",
volume = "178",
pages = "268--275",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "2-3",

}

TY - JOUR

T1 - Neuroendocrine response to intravenous citalopram in healthy control subjects

T2 - Pharmacokinetic influences

AU - Lotrich, Francis E.

AU - Bies, Robert

AU - Muldoon, Matthew F.

AU - Manuck, Stephen B.

AU - Smith, Gwenn S.

AU - Pollock, Bruce G.

PY - 2005/3

Y1 - 2005/3

N2 - 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 (AUC150) 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 AUC150 (prolactin r 2=0.23, P2=0.3, P150 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.

AB - 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 (AUC150) 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 AUC150 (prolactin r 2=0.23, P2=0.3, P150 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.

KW - Citalopram

KW - Cortisol

KW - Neuroendocrine challenge

KW - Pharmacokinetic

KW - Prolactin

UR - http://www.scopus.com/inward/record.url?scp=15244347228&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15244347228&partnerID=8YFLogxK

U2 - 10.1007/s00213-004-2006-4

DO - 10.1007/s00213-004-2006-4

M3 - Article

VL - 178

SP - 268

EP - 275

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 2-3

ER -