A descriptive systematic review of salivary therapeutic drug monitoring in neonates and infants

Laura Hutchinson, Marlene Sinclair, Bernadette Reid, Kathryn Burnett, Bridgeen Callan

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)
38 Downloads (Pure)


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.

Databases 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 TDM 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.

Twenty‐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. Any compound with an acid dissociation constant (pKa) within physiological range (pH 6–8) gave a more varied response.

There 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.
Original languageEnglish
Pages (from-to)1089-1108
Number of pages20
JournalBritish Journal of Clinical Pharmacology
Issue number6
Early online date25 Mar 2018
Publication statusPublished (in print/issue) - 24 May 2018


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


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