High feasibility of salivary therapeutic drug monitoring in linezolid, but lower feasibility in tedizolid: a single-dose study in healthy subjects and a monocentric prospective exploratory study in patients who received linezolid

Salivary therapeutic drug monitoring (TDM) offers the potential to reduce the risks, burden, time and costs of blood-based TDM, but its feasibility for use with oxazolidinone antibiotics and the influence of food intake remain unknown. We conducted a healthy subject study with 12 healthy participant...

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Veröffentlicht in:Journal of antimicrobial chemotherapy Jg. 80; H. 8; S. 2080
Hauptverfasser: Kawasuji, Hitoshi, Tsuji, Yasuhiro, Miyaki, Keiko, Aoyama, Takahiko, Kurosaki, Fumihiro, Ezaki, Masayoshi, Koshiyama, Yuki, Takegoshi, Yusuke, Kaneda, Makito, Murai, Yushi, Kimoto, Kou, Nagaoka, Kentaro, Yamamoto, Yoshihiro
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England 01.08.2025
Schlagworte:
Adult
Aged
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - pharmacokinetics
Chromatography, High Pressure Liquid
Drug Monitoring - methods
Feasibility Studies
Female
Healthy Volunteers
Humans
Linezolid - administration & dosage
Linezolid - pharmacokinetics
Male
Middle Aged
Oxazolidinones - administration & dosage
Oxazolidinones - pharmacokinetics
Prospective Studies
Saliva - chemistry
Tetrazoles - administration & dosage
Tetrazoles - pharmacokinetics
Young Adult
ISSN:1460-2091, 1460-2091
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Zusammenfassung:Salivary therapeutic drug monitoring (TDM) offers the potential to reduce the risks, burden, time and costs of blood-based TDM, but its feasibility for use with oxazolidinone antibiotics and the influence of food intake remain unknown. We conducted a healthy subject study with 12 healthy participants. Linezolid and tedizolid were intravenously administered to 6 participants each. Saliva and peripheral venous blood samples were taken simultaneously at 12 time points and their correlations were evaluated, including a determination of whether these correlations were sustained after food intake. A monocentric prospective exploratory study was then conducted in 10 patients. Total and unbound serum and saliva concentrations were measured using high-performance liquid chromatography. In healthy participants administered linezolid, individual concentration-time curves for saliva were similar to those for serum (total and unbound), but the saliva and serum concentration-time curves differed for tedizolid. Saliva 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. Food intake did not influence the correlations in linezolid. In the exploratory study in 10 patients administered linezolid, saliva concentrations correlated with total or unbound serum concentrations in both non-haemodialysis (n = 7) and haemodialysis (n = 3) patients, irrespective of dosages, administration routes, timing or eating and drinking restrictions. Salivary TDM is a promising alternative to conventional serum sampling for linezolid but is less feasible for tedizolid.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1460-2091
1460-2091
DOI:10.1093/jac/dkaf169