High feasibility of salivary therapeutic drug monitoring in linezolid, but less in tedizolid: A single-dose study in healthy subjects

Abstract

BackgroundSalivary therapeutic drug monitoring (TDM) offers the potential to reduce the risks, burden, time, and costs of blood-based TDM, but its feasibility in oxazolidinone antibiotics and the influence of food intake remain unknown.MethodsA total of 12 healthy volunteers participated in this study. Linezolid and tedizolid were intravenously administered to 6 participants each. Saliva samples were taken at 15 time points and peripheral venous blood samples were also taken at 12 time points simultaneously with saliva. Total and unbound serum and saliva concentrations of linezolid and tedizolid were measured using high-performance liquid chromatography.ResultsIndividual concentration–time curves in saliva versus serum (total and unbound) were similar in linezolid, but different in tedizolid. Saliva concentrations were significantly correlated with total and unbound serum concentrations in both agents. However, concentrations in each case and area under the concentration–time curve from 0 to 10 h (AUC0–10) in saliva were correlated with those in total or unbound serum for linezolid, but not for tedizolid. The mean saliva-to-serum (total and unbound) concentration and AUC0–10ratios were 0.90 and 0.90 in total and 1.09 and 0.99 in unbound. Food intake did not influence these correlations in linezolid.ConclusionsThe analysis of linezolid in saliva is applicable for TDM as a promising alternative to conventional serum sampling without correlation factors, but application of tedizolid is less feasible. Easy sampling using a noninvasive technique may facilitate TDM even in underdeveloped countries with limited resources and specific patient categories.