Optimal kinetic exposures for classic and candidate antitrypanosomals.

ABSTRACT:

Objectives

Efficacy is determined not only by size, but also by shape, of drug exposure. Here the critical importance of the temporal pattern of drug concentrations (pharmacokinetic profile) is examined for antitrypanosomals in vitro.

Methods

An in vitro hollow-fibre cartridge system was used to study contrasting drug profiles with four clinically used agents and two experimental candidates against the deadly parasite Trypanosoma brucei. Artificial kinetics were employed intentionally to favour either high peak concentration or sustained duration of drug.

Results

Changing the shape of drug exposure significantly impacted drug efficacy. Suramin, melarsoprol and pentamidine were concentration-driven and therefore more efficacious when applied as short-lived high peaks.

SUBMITTER: Meyer KJ 

PROVIDER: S-EPMC6640303 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature