A descriptive systematic review of salivary TDM in neonates and infants.

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3 Citations (Scopus)

Abstract

Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates. MethodsDatabases were searched up to and including September 2016. Studies were included based on PICO as follows: P: Infants and neonates being treated with any medication, I: Salivary Therapeutic Drug Monitoring vs C: Traditional methods and O: accuracy, advantages/disadvantages and applicability to practice. Compounds were assessed by their physicochemical and pharmacokinetic properties, as well as published quantitative saliva monitoring data. ResultsTwenty-four studies and their respective 13 compounds were investigated. Four neutral and two acidic compounds, oxcarbazepine, primidone, fluconazole, busulfan, theophylline and phenytoin displayed excellent /very good correlation between blood plasma and saliva. Lamotrigine was the only basic compound to show excellent correlation with morphine exhibiting no correlation between saliva and blood plasma. Furthermore, any compound with a pKa within physiological range (pH 6 – 8) gave a more varied response. ConclusionThere is significant potential for infantile saliva testing and in particular, for neutral and weakly acidic compounds. Of the properties investigated, pKa was the most influential with both logP and protein binding having little effect on this correlation. To conclude any compound with a pKa within physiological range (pH 6 – 8) should be considered with extra care, with the extraction and analysis method examined and optimized on a case-by-case basis.
LanguageEnglish
Pages1089-1108
Number of pages20
JournalBritish Journal of Clinical Pharmacology
Volume84
Issue number6
Early online date14 Feb 2018
DOIs
Publication statusPublished - 30 Jun 2018

Fingerprint

Drug Monitoring
Saliva
Newborn Infant
Primidone
Busulfan
Fluconazole
Phenytoin
Theophylline
Protein Binding
Morphine
Pharmacokinetics

Keywords

  • Therapeutic Drug monitoring (TDM)
  • saliva
  • physicochemical properties
  • pharmacokinetic parameters
  • infants
  • paediatric
  • systematic review

Cite this

@article{eff60c2a0fd74b89bb0c045f0c146cb0,
title = "A descriptive systematic review of salivary TDM in neonates and infants.",
abstract = "Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates. MethodsDatabases were searched up to and including September 2016. Studies were included based on PICO as follows: P: Infants and neonates being treated with any medication, I: Salivary Therapeutic Drug Monitoring vs C: Traditional methods and O: accuracy, advantages/disadvantages and applicability to practice. Compounds were assessed by their physicochemical and pharmacokinetic properties, as well as published quantitative saliva monitoring data. ResultsTwenty-four studies and their respective 13 compounds were investigated. Four neutral and two acidic compounds, oxcarbazepine, primidone, fluconazole, busulfan, theophylline and phenytoin displayed excellent /very good correlation between blood plasma and saliva. Lamotrigine was the only basic compound to show excellent correlation with morphine exhibiting no correlation between saliva and blood plasma. Furthermore, any compound with a pKa within physiological range (pH 6 – 8) gave a more varied response. ConclusionThere is significant potential for infantile saliva testing and in particular, for neutral and weakly acidic compounds. Of the properties investigated, pKa was the most influential with both logP and protein binding having little effect on this correlation. To conclude any compound with a pKa within physiological range (pH 6 – 8) should be considered with extra care, with the extraction and analysis method examined and optimized on a case-by-case basis.",
keywords = "Therapeutic Drug monitoring (TDM), saliva, physicochemical properties, pharmacokinetic parameters, infants, paediatric, systematic review",
author = "Laura Hutchinson and M Sinclair and Bernie Reid and Kathryn Burnett and Bridgeen Callan",
note = "Compliant in UIR; evidence uploaded to 'Other files'",
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doi = "10.1111/bcp.13553",
language = "English",
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pages = "1089--1108",
journal = "British Journal of Clinical Pharmacology",
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T1 - A descriptive systematic review of salivary TDM in neonates and infants.

AU - Hutchinson, Laura

AU - Sinclair, M

AU - Reid, Bernie

AU - Burnett, Kathryn

AU - Callan, Bridgeen

N1 - Compliant in UIR; evidence uploaded to 'Other files'

PY - 2018/6/30

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N2 - Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates. MethodsDatabases were searched up to and including September 2016. Studies were included based on PICO as follows: P: Infants and neonates being treated with any medication, I: Salivary Therapeutic Drug Monitoring vs C: Traditional methods and O: accuracy, advantages/disadvantages and applicability to practice. Compounds were assessed by their physicochemical and pharmacokinetic properties, as well as published quantitative saliva monitoring data. ResultsTwenty-four studies and their respective 13 compounds were investigated. Four neutral and two acidic compounds, oxcarbazepine, primidone, fluconazole, busulfan, theophylline and phenytoin displayed excellent /very good correlation between blood plasma and saliva. Lamotrigine was the only basic compound to show excellent correlation with morphine exhibiting no correlation between saliva and blood plasma. Furthermore, any compound with a pKa within physiological range (pH 6 – 8) gave a more varied response. ConclusionThere is significant potential for infantile saliva testing and in particular, for neutral and weakly acidic compounds. Of the properties investigated, pKa was the most influential with both logP and protein binding having little effect on this correlation. To conclude any compound with a pKa within physiological range (pH 6 – 8) should be considered with extra care, with the extraction and analysis method examined and optimized on a case-by-case basis.

AB - Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates. MethodsDatabases were searched up to and including September 2016. Studies were included based on PICO as follows: P: Infants and neonates being treated with any medication, I: Salivary Therapeutic Drug Monitoring vs C: Traditional methods and O: accuracy, advantages/disadvantages and applicability to practice. Compounds were assessed by their physicochemical and pharmacokinetic properties, as well as published quantitative saliva monitoring data. ResultsTwenty-four studies and their respective 13 compounds were investigated. Four neutral and two acidic compounds, oxcarbazepine, primidone, fluconazole, busulfan, theophylline and phenytoin displayed excellent /very good correlation between blood plasma and saliva. Lamotrigine was the only basic compound to show excellent correlation with morphine exhibiting no correlation between saliva and blood plasma. Furthermore, any compound with a pKa within physiological range (pH 6 – 8) gave a more varied response. ConclusionThere is significant potential for infantile saliva testing and in particular, for neutral and weakly acidic compounds. Of the properties investigated, pKa was the most influential with both logP and protein binding having little effect on this correlation. To conclude any compound with a pKa within physiological range (pH 6 – 8) should be considered with extra care, with the extraction and analysis method examined and optimized on a case-by-case basis.

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