Applications of Exhaled Breath Condensate Analysis for Drug Monitoring and Bioequivalence Study of Inhaled Drugs

Abstract

The exhaled breath condensate (EBC) presents a simple and non-invasive alternative approach for bioequivalence assessments and therapeutic drug monitoring of inhaled drugs. EBC better represents the drug at the site of action and eliminates the possibility of the contribution of a swallowed portion of the dose when systemic bioavailability is used for assessment. This review summarizes the recently reported analytical methods for the quantification of drugs in EBC. It also discusses the difficulties in the bioequivalence evaluation criteria of generic orally inhaled drug products suggested by various regulatory agencies that may be eliminated using the EBC analysis approach.

The Bioavailability of Drugs—The Current State of Knowledge

“…This study involves comparing the concentration of the two drugs under examination in the blood or other body fluids. These studies aim to determine whether two drug preparations are pharmaceutically equivalent and exhibit similar therapeutic effects [76]. In vivo procedures include pharmacodynamic studies that evaluate the way a drug impacts the human organism following delivery.…”

A new method for investigating bioequivalence of inhaled formulations: A pilot study on salbutamol

“…The limit of detection (LOD), lower limit of quantification (LLOQ), linear range, precision, and extraction recovery (ER) of the method were assessed based on the US FDA ( 4 ) and ICH Registration ( 35 ) guidelines. A matrix–matched method was used for construction of the calibration curve.…”

“…For the generic formulations of a reference product registered in China, they use a similar approach to European countries, and for the non-registered reference products, a new drug application is mandatory ( 3 ). These criteria are briefly reviewed in a recent work ( 4 ).…”

Utilizing a nanocomposite aerogel grafted with Fe3O4@GO for the extraction and determination of metoprolol in exhaled breath condensate

“…24 Exhaled breath condensate (EBC), as newly used biological sample type, has attracted increasing attention in recent years. [25][26][27][28] It possesses both volatile and non-volatile analytes of various sizes, from small metal ions to genes and proteins. EBC has been introduced as an alternative biological sample type due to its less complicated matrix, non-invasive sampling procedure compared to blood samples, more prominent compliance from patients, and as it permits coordinated sampling injection into the analyzer, with no need for a skilled individual to gather the EBC, and the plausibility of providing as many as required samples per day.…”