Utility of sparse concentration sampling for citalopram in elderly clinical trial subjects

Robert Bies, Yan Feng, Francis E. Lotrich, Margaret A. Kirshner, Steven Roose, David J. Kupfer, Bruce G. Pollock

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The objective of this study was to evaluate whether the disposition of the selective serotonin reuptake inhibitor, citalopram, could be robustly captured using 1 to 2 concentration samples per subject in 106 patients participating in 2 clinical trials. Nonlinear mixed-effects modeling was used to evaluate the pharmacokinetic parameters describing citalopram's disposition. Both a prior established 2-compartment model and a de novo 1-compartment pharmacokinetic model were used. Covariates assessed were concomitant medications, race, sex, age (22-93 years), and weight. Covariates affecting disposition were assessed separately and then combined in a stepwise manner. Pharmacokinetic characteristics of citalopram were well captured using this sparse sampling design. Two covariates (age and weight) had a significant effect on the clearance and volume of distribution in both the 1- and 2-compartment pharmacokinetic models. Clearance decreased 0.23 L/h for every year of age and increased 0.14 L/h per kilogram body weight. It was concluded that hyper-sparse sampling designs are adequate to support population pharmacokinetic analysis in clinically treated populations. This is particularly valuable for populations such as the elderly, who are not typically available for pharmacokinetic studies.

Original languageEnglish (US)
Pages (from-to)1352-1359
Number of pages8
JournalJournal of Clinical Pharmacology
Volume44
Issue number12
DOIs
StatePublished - Dec 2004
Externally publishedYes

Fingerprint

Citalopram
Pharmacokinetics
Clinical Trials
Population
Weights and Measures
Serotonin Uptake Inhibitors
Body Weight

Keywords

  • Citalopram
  • Depression
  • Elderly patients
  • Geriatrics
  • Pharmacokinetic studies
  • Selective serotonin reuptake inhibitors

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Bies, R., Feng, Y., Lotrich, F. E., Kirshner, M. A., Roose, S., Kupfer, D. J., & Pollock, B. G. (2004). Utility of sparse concentration sampling for citalopram in elderly clinical trial subjects. Journal of Clinical Pharmacology, 44(12), 1352-1359. https://doi.org/10.1177/0091270004269647

Utility of sparse concentration sampling for citalopram in elderly clinical trial subjects. / Bies, Robert; Feng, Yan; Lotrich, Francis E.; Kirshner, Margaret A.; Roose, Steven; Kupfer, David J.; Pollock, Bruce G.

In: Journal of Clinical Pharmacology, Vol. 44, No. 12, 12.2004, p. 1352-1359.

Research output: Contribution to journalArticle

Bies, R, Feng, Y, Lotrich, FE, Kirshner, MA, Roose, S, Kupfer, DJ & Pollock, BG 2004, 'Utility of sparse concentration sampling for citalopram in elderly clinical trial subjects', Journal of Clinical Pharmacology, vol. 44, no. 12, pp. 1352-1359. https://doi.org/10.1177/0091270004269647
Bies, Robert ; Feng, Yan ; Lotrich, Francis E. ; Kirshner, Margaret A. ; Roose, Steven ; Kupfer, David J. ; Pollock, Bruce G. / Utility of sparse concentration sampling for citalopram in elderly clinical trial subjects. In: Journal of Clinical Pharmacology. 2004 ; Vol. 44, No. 12. pp. 1352-1359.
@article{955b3cb0bd9e4c64b0465712e494d23b,
title = "Utility of sparse concentration sampling for citalopram in elderly clinical trial subjects",
abstract = "The objective of this study was to evaluate whether the disposition of the selective serotonin reuptake inhibitor, citalopram, could be robustly captured using 1 to 2 concentration samples per subject in 106 patients participating in 2 clinical trials. Nonlinear mixed-effects modeling was used to evaluate the pharmacokinetic parameters describing citalopram's disposition. Both a prior established 2-compartment model and a de novo 1-compartment pharmacokinetic model were used. Covariates assessed were concomitant medications, race, sex, age (22-93 years), and weight. Covariates affecting disposition were assessed separately and then combined in a stepwise manner. Pharmacokinetic characteristics of citalopram were well captured using this sparse sampling design. Two covariates (age and weight) had a significant effect on the clearance and volume of distribution in both the 1- and 2-compartment pharmacokinetic models. Clearance decreased 0.23 L/h for every year of age and increased 0.14 L/h per kilogram body weight. It was concluded that hyper-sparse sampling designs are adequate to support population pharmacokinetic analysis in clinically treated populations. This is particularly valuable for populations such as the elderly, who are not typically available for pharmacokinetic studies.",
keywords = "Citalopram, Depression, Elderly patients, Geriatrics, Pharmacokinetic studies, Selective serotonin reuptake inhibitors",
author = "Robert Bies and Yan Feng and Lotrich, {Francis E.} and Kirshner, {Margaret A.} and Steven Roose and Kupfer, {David J.} and Pollock, {Bruce G.}",
year = "2004",
month = "12",
doi = "10.1177/0091270004269647",
language = "English (US)",
volume = "44",
pages = "1352--1359",
journal = "Journal of Clinical Pharmacology",
issn = "0091-2700",
publisher = "SAGE Publications Inc.",
number = "12",

}

TY - JOUR

T1 - Utility of sparse concentration sampling for citalopram in elderly clinical trial subjects

AU - Bies, Robert

AU - Feng, Yan

AU - Lotrich, Francis E.

AU - Kirshner, Margaret A.

AU - Roose, Steven

AU - Kupfer, David J.

AU - Pollock, Bruce G.

PY - 2004/12

Y1 - 2004/12

N2 - The objective of this study was to evaluate whether the disposition of the selective serotonin reuptake inhibitor, citalopram, could be robustly captured using 1 to 2 concentration samples per subject in 106 patients participating in 2 clinical trials. Nonlinear mixed-effects modeling was used to evaluate the pharmacokinetic parameters describing citalopram's disposition. Both a prior established 2-compartment model and a de novo 1-compartment pharmacokinetic model were used. Covariates assessed were concomitant medications, race, sex, age (22-93 years), and weight. Covariates affecting disposition were assessed separately and then combined in a stepwise manner. Pharmacokinetic characteristics of citalopram were well captured using this sparse sampling design. Two covariates (age and weight) had a significant effect on the clearance and volume of distribution in both the 1- and 2-compartment pharmacokinetic models. Clearance decreased 0.23 L/h for every year of age and increased 0.14 L/h per kilogram body weight. It was concluded that hyper-sparse sampling designs are adequate to support population pharmacokinetic analysis in clinically treated populations. This is particularly valuable for populations such as the elderly, who are not typically available for pharmacokinetic studies.

AB - The objective of this study was to evaluate whether the disposition of the selective serotonin reuptake inhibitor, citalopram, could be robustly captured using 1 to 2 concentration samples per subject in 106 patients participating in 2 clinical trials. Nonlinear mixed-effects modeling was used to evaluate the pharmacokinetic parameters describing citalopram's disposition. Both a prior established 2-compartment model and a de novo 1-compartment pharmacokinetic model were used. Covariates assessed were concomitant medications, race, sex, age (22-93 years), and weight. Covariates affecting disposition were assessed separately and then combined in a stepwise manner. Pharmacokinetic characteristics of citalopram were well captured using this sparse sampling design. Two covariates (age and weight) had a significant effect on the clearance and volume of distribution in both the 1- and 2-compartment pharmacokinetic models. Clearance decreased 0.23 L/h for every year of age and increased 0.14 L/h per kilogram body weight. It was concluded that hyper-sparse sampling designs are adequate to support population pharmacokinetic analysis in clinically treated populations. This is particularly valuable for populations such as the elderly, who are not typically available for pharmacokinetic studies.

KW - Citalopram

KW - Depression

KW - Elderly patients

KW - Geriatrics

KW - Pharmacokinetic studies

KW - Selective serotonin reuptake inhibitors

UR - http://www.scopus.com/inward/record.url?scp=8744240474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8744240474&partnerID=8YFLogxK

U2 - 10.1177/0091270004269647

DO - 10.1177/0091270004269647

M3 - Article

VL - 44

SP - 1352

EP - 1359

JO - Journal of Clinical Pharmacology

JF - Journal of Clinical Pharmacology

SN - 0091-2700

IS - 12

ER -