Measurement of isoniazid in tuberculosis patients using finger sweat with creatinine normalisation: A controlled administration study

Int J Antimicrob Agents. 2024 Aug;64(2):107231. doi: 10.1016/j.ijantimicag.2024.107231. Epub 2024 Jun 25.

Abstract

Background: Insufficient exposure and poor compliance with anti-tuberculosis (TB) medications are risk factors for treatment failure and the development of drug resistance. Measurement of drugs in biological samples, such as blood and saliva, can be used to assess adherence and make dose adjustments by therapeutic drug monitoring (TDM). Finger sweat testing is a convenient and non-invasive method to monitor patients.

Objectives: To assess the feasibility of finger sweat testing for medication adherence and as a semi-quantitative tool for TDM analysis.

Methods: Ten patients provided finger sweat, blood and saliva samples following a controlled dose of isoniazid. Samples were analysed by liquid chromatography-mass spectrometry.

Results: Isoniazid can be detected in finger sweat 1-6 h following administration at typically prescribed dosages. The normalisation of isoniazid to creatinine increases the correlation between finger sweat and serum isoniazid concentration and provides a means to account for inconsistent sample volumes.

Conclusion: We describe the time-course measurement of isoniazid (or drug-to-creatinine ratio) in finger sweat compared to the pharmacokinetic profile in blood for the first time. This technique, adaptable for other drugs, could reduce the burden on clinics and improve patient experience.

Keywords: Adherence; Creatinine; Finger sweat; Non-invasive; Tuberculosis.

MeSH terms

  • Adult
  • Antitubercular Agents* / administration & dosage
  • Antitubercular Agents* / pharmacokinetics
  • Chromatography, Liquid / methods
  • Creatinine* / blood
  • Drug Monitoring* / methods
  • Female
  • Humans
  • Isoniazid* / administration & dosage
  • Isoniazid* / pharmacokinetics
  • Male
  • Mass Spectrometry
  • Medication Adherence
  • Middle Aged
  • Saliva / chemistry
  • Sweat* / chemistry
  • Tuberculosis* / drug therapy
  • Young Adult

Substances

  • Isoniazid
  • Antitubercular Agents
  • Creatinine