Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Rapid In Vitro Assessment of Antimicrobial Drug Effect Bridging Clinically Relevant Pharmacokinetics: A Comprehensive Methodology

Version 1 : Received: 13 April 2023 / Approved: 13 April 2023 / Online: 13 April 2023 (09:36:01 CEST)

A peer-reviewed article of this Preprint also exists.

Nikolaou, M.; Tam, V.H. Rapid In Vitro Assessment of Antimicrobial Drug Effect Bridging Clinically Relevant Pharmacokinetics: A Comprehensive Methodology. Pharmaceutics 2023, 15, 1671. Nikolaou, M.; Tam, V.H. Rapid In Vitro Assessment of Antimicrobial Drug Effect Bridging Clinically Relevant Pharmacokinetics: A Comprehensive Methodology. Pharmaceutics 2023, 15, 1671.

Abstract

Rapid in vitro assessment of antimicrobial drug efficacy under clinically relevant pharmacokinetic conditions is an essential element of both drug development and clinical use. Here we present an overview of a novel integrated methodology for rapid assessment of such efficacy, particularly against emergence of resistant bacterial strains, as jointly researched by the authors in recent years. This methodology enables rapid in vitro assessment of antimicrobial efficacy of a single or multiple drugs in combination, following clinically relevant pharmacokinetics. The proposed methodology entails (a) automated collection of longitudinal time-kill data in an optical-density instrument; (b) processing of collected time-kill data with the aid of a mathematical model to de-termine optimal dosing regimens under clinically relevant pharmacokinetics for a single or mul-tiple drugs; and (c) in vitro validation of promising dosing regimens in a hollow fiber system. Proof-of-concept of this methodology through a number of in vitro studies is discussed. Future directions for refinement of optimal data collection and processing are discussed.

Keywords

Pharmacokinetics; Pharmacodynamics; Antimicrobials; Antimicrobial resistance; Combination therapy; Mathematical modeling

Subject

Medicine and Pharmacology, Medicine and Pharmacology

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