Saliva as a matrix for therapeutic drug monitoring and disease biomarkers in children and adolescents.

Saliva is a more accessible, less stressful, and less expensive biological matrix than blood, and may be applicable in therapeutic drug monitoring (TDM). Saliva concentrations reflect the pharmacologically active unbound drug. This review provides the latest information on saliva as a matrix for therapeutic drug monitoring (TDM) and biomarker determination in infants, children, and adolescents. Literature was searched up to October 2024 using the PubMed database and 64 studies were included in TDM, steroids, supplements, disease biomarkers, dentistry, genetics, and other categories. Unstimulated saliva was collected using cotton swabs or synthetic fiber rolls, as expectorated or freely flowing saliva, and stimulated by chewing on a rubber band or paraffin block. For drug determination, saliva was purified by centrifugation. Protein precipitation or extraction was rarely used. Saliva volumes for analyses were low (2.5-10 µL). Chromatographic methods and immunoassays were used for drug determination. Commercially available kits were applied for saliva hormones analysis or DNA quantification. For some antibiotics, antiepileptics, mood-stabilizers, analgesics, and immunosuppressants, saliva-plasma correlations were found. Saliva has the potential for fentanyl and prednisolone TDM in the pediatric population and for congenital adrenal hyperplasia monitoring. Salivary cortisol measurements in adolescents may play a role in sociological and psychological responses to stress, whereas in infants may reflect the depressive symptoms and higher cortisol levels of mothers. Saliva may help in diagnosing Keratoconus, pediatric-onset multiple sclerosis, sleep disorders, and quantitative behavioral difficulties. Saliva sampling depends on patient compliance. The samples may be contaminated with blood from gingival bleeding.