Relevance of assessing drug concentration exposure in pharmacogenetic and imaging studies

Francis E. Lotrich, Robert R. Bies, Gwenn Smith, Bruce G. Pollock

Research output: Contribution to journalArticle

Abstract

Pharmacodynamic differences are difficult to interpret without drug concentration data. In particular, variability in drug exposure may confound the interpretation of pharmacogenetic, therapeutic outcome, and neuroimaging studies. Inter-individual variability in concentrations can be quite high due to variable adherence and pharmacokinetics. For example, clearance may be influenced by genetics, drug interactions, age and illness. We review findings that acute responses to selective serotonin reuptake inhibitors can have a concentration-response relationship using positron emission tomography and neuroendocrine measures. We also present preliminary evidence that the concentration-response relationship for paroxetine is influenced by genotypic differences at the serotonin transporter promoter. In large clinical studies, the accurate assessment of drug exposure can be challenging, with several techniques used to assess exposure. Population pharmacokinetics (Pop PK) is a method that is ideally suited for analysing concentration data from large trials because both patient-specific and population parameters can be determined with only a small number of plasma samples per patient. As opposed to relying on prescribed doses or a single trough level, the ability to determine more accurately exposure with Pop PK reduces the heterogeneity introduced by exposure variability. Pop PK hierarchic Bayesian approaches have been effective for characterizing anticonvulsants, antibiotics, antineoplastics and antiarrhythmics. We have recently successfully incorporated these pop PK analyses into routine assessments of elderly patients in clinical trials of selective serotonin reuptake inhibitors (SSRIs) and second generation antipsychotics. For the design and interpretation of neuroimaging, pharmacogenetic, and behavioural studies, the assessment of drug concentration exposure is therefore feasible and has potentially important ramifications.

Original languageEnglish (US)
Pages (from-to)33-40
Number of pages8
JournalJournal of Psychopharmacology
Volume20
Issue number4 SUPPL.
DOIs
StatePublished - Jul 2006
Externally publishedYes

Fingerprint

Pharmacokinetics
Serotonin Uptake Inhibitors
Neuroimaging
Pharmaceutical Preparations
Population
Antineoplastic Antibiotics
Paroxetine
Serotonin Plasma Membrane Transport Proteins
Bayes Theorem
Pharmacogenetics
Drug Interactions
Positron-Emission Tomography
Anticonvulsants
Antipsychotic Agents
Outcome Assessment (Health Care)
Clinical Trials
Pharmacogenomic Testing
Therapeutics

Keywords

  • Concentration
  • Neuroimaging
  • Pharmacogenetics
  • Population pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Neuroscience(all)

Cite this

Relevance of assessing drug concentration exposure in pharmacogenetic and imaging studies. / Lotrich, Francis E.; Bies, Robert R.; Smith, Gwenn; Pollock, Bruce G.

In: Journal of Psychopharmacology, Vol. 20, No. 4 SUPPL., 07.2006, p. 33-40.

Research output: Contribution to journalArticle

Lotrich, Francis E. ; Bies, Robert R. ; Smith, Gwenn ; Pollock, Bruce G. / Relevance of assessing drug concentration exposure in pharmacogenetic and imaging studies. In: Journal of Psychopharmacology. 2006 ; Vol. 20, No. 4 SUPPL. pp. 33-40.
@article{982935a91ff94121a2d12ee1eb098469,
title = "Relevance of assessing drug concentration exposure in pharmacogenetic and imaging studies",
abstract = "Pharmacodynamic differences are difficult to interpret without drug concentration data. In particular, variability in drug exposure may confound the interpretation of pharmacogenetic, therapeutic outcome, and neuroimaging studies. Inter-individual variability in concentrations can be quite high due to variable adherence and pharmacokinetics. For example, clearance may be influenced by genetics, drug interactions, age and illness. We review findings that acute responses to selective serotonin reuptake inhibitors can have a concentration-response relationship using positron emission tomography and neuroendocrine measures. We also present preliminary evidence that the concentration-response relationship for paroxetine is influenced by genotypic differences at the serotonin transporter promoter. In large clinical studies, the accurate assessment of drug exposure can be challenging, with several techniques used to assess exposure. Population pharmacokinetics (Pop PK) is a method that is ideally suited for analysing concentration data from large trials because both patient-specific and population parameters can be determined with only a small number of plasma samples per patient. As opposed to relying on prescribed doses or a single trough level, the ability to determine more accurately exposure with Pop PK reduces the heterogeneity introduced by exposure variability. Pop PK hierarchic Bayesian approaches have been effective for characterizing anticonvulsants, antibiotics, antineoplastics and antiarrhythmics. We have recently successfully incorporated these pop PK analyses into routine assessments of elderly patients in clinical trials of selective serotonin reuptake inhibitors (SSRIs) and second generation antipsychotics. For the design and interpretation of neuroimaging, pharmacogenetic, and behavioural studies, the assessment of drug concentration exposure is therefore feasible and has potentially important ramifications.",
keywords = "Concentration, Neuroimaging, Pharmacogenetics, Population pharmacokinetics",
author = "Lotrich, {Francis E.} and Bies, {Robert R.} and Gwenn Smith and Pollock, {Bruce G.}",
year = "2006",
month = "7",
doi = "10.1177/1359786806066044",
language = "English (US)",
volume = "20",
pages = "33--40",
journal = "Journal of Psychopharmacology",
issn = "0269-8811",
publisher = "SAGE Publications Ltd",
number = "4 SUPPL.",

}

TY - JOUR

T1 - Relevance of assessing drug concentration exposure in pharmacogenetic and imaging studies

AU - Lotrich, Francis E.

AU - Bies, Robert R.

AU - Smith, Gwenn

AU - Pollock, Bruce G.

PY - 2006/7

Y1 - 2006/7

N2 - Pharmacodynamic differences are difficult to interpret without drug concentration data. In particular, variability in drug exposure may confound the interpretation of pharmacogenetic, therapeutic outcome, and neuroimaging studies. Inter-individual variability in concentrations can be quite high due to variable adherence and pharmacokinetics. For example, clearance may be influenced by genetics, drug interactions, age and illness. We review findings that acute responses to selective serotonin reuptake inhibitors can have a concentration-response relationship using positron emission tomography and neuroendocrine measures. We also present preliminary evidence that the concentration-response relationship for paroxetine is influenced by genotypic differences at the serotonin transporter promoter. In large clinical studies, the accurate assessment of drug exposure can be challenging, with several techniques used to assess exposure. Population pharmacokinetics (Pop PK) is a method that is ideally suited for analysing concentration data from large trials because both patient-specific and population parameters can be determined with only a small number of plasma samples per patient. As opposed to relying on prescribed doses or a single trough level, the ability to determine more accurately exposure with Pop PK reduces the heterogeneity introduced by exposure variability. Pop PK hierarchic Bayesian approaches have been effective for characterizing anticonvulsants, antibiotics, antineoplastics and antiarrhythmics. We have recently successfully incorporated these pop PK analyses into routine assessments of elderly patients in clinical trials of selective serotonin reuptake inhibitors (SSRIs) and second generation antipsychotics. For the design and interpretation of neuroimaging, pharmacogenetic, and behavioural studies, the assessment of drug concentration exposure is therefore feasible and has potentially important ramifications.

AB - Pharmacodynamic differences are difficult to interpret without drug concentration data. In particular, variability in drug exposure may confound the interpretation of pharmacogenetic, therapeutic outcome, and neuroimaging studies. Inter-individual variability in concentrations can be quite high due to variable adherence and pharmacokinetics. For example, clearance may be influenced by genetics, drug interactions, age and illness. We review findings that acute responses to selective serotonin reuptake inhibitors can have a concentration-response relationship using positron emission tomography and neuroendocrine measures. We also present preliminary evidence that the concentration-response relationship for paroxetine is influenced by genotypic differences at the serotonin transporter promoter. In large clinical studies, the accurate assessment of drug exposure can be challenging, with several techniques used to assess exposure. Population pharmacokinetics (Pop PK) is a method that is ideally suited for analysing concentration data from large trials because both patient-specific and population parameters can be determined with only a small number of plasma samples per patient. As opposed to relying on prescribed doses or a single trough level, the ability to determine more accurately exposure with Pop PK reduces the heterogeneity introduced by exposure variability. Pop PK hierarchic Bayesian approaches have been effective for characterizing anticonvulsants, antibiotics, antineoplastics and antiarrhythmics. We have recently successfully incorporated these pop PK analyses into routine assessments of elderly patients in clinical trials of selective serotonin reuptake inhibitors (SSRIs) and second generation antipsychotics. For the design and interpretation of neuroimaging, pharmacogenetic, and behavioural studies, the assessment of drug concentration exposure is therefore feasible and has potentially important ramifications.

KW - Concentration

KW - Neuroimaging

KW - Pharmacogenetics

KW - Population pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=33750087310&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750087310&partnerID=8YFLogxK

U2 - 10.1177/1359786806066044

DO - 10.1177/1359786806066044

M3 - Article

C2 - 16785268

AN - SCOPUS:33750087310

VL - 20

SP - 33

EP - 40

JO - Journal of Psychopharmacology

JF - Journal of Psychopharmacology

SN - 0269-8811

IS - 4 SUPPL.

ER -