Saliva as a TDM Matrix and Its Application in the Model-Informed Precision Dosing

This study reviews the main points of saliva as a therapeutic drug monitoring (TDM) matrix, its advantages and limitations, the methods of saliva sample collection and testing, the types of drugs in saliva TDM, and the methods of establishing saliva population pharmacokinetic (Pop PK) models, as well as summarizes the experiences and limitations, to provide references to carry out related studies. The PubMed database was systematically searched for studies on the topic of saliva as a matrix for drug TDM. The literature was screened according to the established inclusion and exclusion criteria, and relevant data were extracted and summarized. The systematic review ultimately screened 112 articles involving relevant studies on 73 drugs, of which studies on 53 drugs supported saliva as a matrix for TDM; studies on 13 drugs did not support it; and the results of studies on seven drugs were inconsistent, with conflicting results regarding whether they supported salivary TDM or not. The study steps for Pop PK modeling based on saliva concentrations are summarized, and representative drugs for which Pop PK models incorporating both plasma and saliva concentrations have been established are listed. Saliva TDM, as a new exploration and attempt, has been confirmed to be feasible for some drugs in the current study, and is expected to be applied to the clinic in the future; Pop PK modeling based on saliva TDM for precision drug delivery has only been initially attempted for some drugs, and its application has yet to be verified in clinical studies.