Therapeutic drug monitoring in exhaled breath

The recent publication “Volatile Biomarkers for Human Health: From Nature to Artificial Senses”, edited by Hossam Haick, provides a comprehensive overview about the principles of basic pharmacokinetics, focusing on volatile organic compounds (VOCs) and related physiological concepts. Furthermore, it also compiles a list of drugs detected in exhaled breath and presents the necessary analytical tools to monitor drugs and their metabolites.

Fundamentals of TDM in exhaled breath

When a patient takes a drug, the active ingredient must be absorbed by the patients’ body. Only then the drug can develop its effect. After that, it is eliminated or transformed into metabolites and excreted via different pathways (see schematic in Figure 1). Most commonly, drugs are metabolized and excreted by the liver, but other, so called extrahepatic, pathways exist, e.g., through the lung via breath. The elimination of drug metabolites via breath is an underestimated pathway but one that offers huge potential for personalized therapeutic drug monitoring.

Figure 1. LADME is an acronym in pharmacokinetics for processes that affect the drug therapy effect. The processes include the Liberation, the Absorption, Distribution, Metabolism and, finally, the Excretion of the active pharmaceutical ingredient in the body.

In this extrahepatic pathway, drug compounds or drug metabolites are eliminated by permeating the blood-air barrier. Based on their volatility, these molecules can be measured as volatile organic compounds (VOCs), semi-volatile organic compounds (SVOC) or organic compounds with particulate matter (POM). Different technologies can be employed to analyze these molecules. For example, secondary electrospray ionization high-resolution mass spectrometer (SESI-HRMS) can measure VOCs, SVOCs and POMs noninvasively and in real time. Furthermore, breath sampling is convenient for patients.

Pioneering technologies for TDM via breath

To date, two applications rely on TDM via breath. First, an ion mobility spectrometer measures propofol online during anesthesia. Second, DBI-EPIbreath® measures valproic acid, a common antiseizure drug, using the SESI-HRMS platform for therapeutic drug monitoring in people living with epilepsy.

DBI works on solutions for medical research and daily clinical practice by combining SESI-HRMS with advanced machine learning techniques for state-of-the-art breath analysis. Learn more about DBI’s technology & solution.

See the following video about breath research: