ArticleThe Journal of antimicrobial chemotherapy2019
Optimal kinetic exposures for classic and candidate antitrypanosomals.
Article in The Journal of antimicrobial chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- RNA Polymerase 1 inhibitors against African trypanosomesAntimicrobial agents and chemotherapy · 2026Article
- Pharmacokinetics of venetoclax in a patient after whipple pancreaticoduodenectomy.Cancer chemotherapy and pharmacology · 2026Article
- Prophylactic low-dose, bi-weekly benznidazole treatment fails to prevent Trypanosoma cruzi infection in dogs under intense transmission pressure.PLoS neglected tropical diseases · 2022Article
- Article
- Non-invasive monitoring of drug action: A new live in vitro assay design for Chagas' disease drug discovery.PLoS neglected tropical diseases · 2020Article
- Investigation of pyrimidine nucleoside analogues as chemical probes to assess compound effects on the proliferation of Trypanosoma cruzi intracellular parasites.PLoS neglected tropical diseases · 2020Article
- Kinetic Driver of Antibacterial Drugs againstAntimicrobial agents and chemotherapy · 2019Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
objectivesEfficacy 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.
methodsAn 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.
resultsChanging 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. In contrast, difluoromethylornithine (DFMO) was time-driven, and therefore maximally effective as a constant infusion. Kinetic preference was robust over a wide range of drug exposures. Promising clinical candidates SCYX-7158 (acoziborole) and fexinidazole (parent and sulfone) were concentration-driven, suggesting optimal clinical regimens would involve relatively high but intermittent dosing.
conclusionsAntitrypanosomals have an intrinsic pharmacokinetic driver for optimal efficacy, with important implications for clinical management and future candidate development.
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