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

Summary

Introduction

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.

Methods

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 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.

Results

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. Furthermore, any compound with a pKa within physiological range (pH 6 – 8) gave a more varied response.

Conclusion

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.

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