Mitochondria as targets of drug toxicity: Lessons from the R118 phase I experience

Solely the dose determines that a thing is not a poison. —Paracelsus 1493–15411 Low Wang et al. report the results of the phase I program for R118 in this issue.2 R118 was designed as an activator of adenosine monophosphate activated protein kinase (AMPK) to treat claudication. The single ascending...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2015-11, Vol.98 (5), p.464-466
Main Authors: Brass, EP, Hoppel, CL
Format: Article
Language:English
Subjects:
Drug Delivery Systems - methods
Drugs, Investigational - administration & dosage
Drugs, Investigational - adverse effects
Electron Transport Complex I - antagonists & inhibitors
Female
Humans
Male
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Summary:Solely the dose determines that a thing is not a poison. —Paracelsus 1493–15411 Low Wang et al. report the results of the phase I program for R118 in this issue.2 R118 was designed as an activator of adenosine monophosphate activated protein kinase (AMPK) to treat claudication. The single ascending dose study in healthy subjects was characterized by an unacceptable number of serious adverse events and substantial risk to the participants. The probable mitochondrial mechanism underlying these adverse events suggests important lessons for future drug development.
ISSN:0009-9236
1532-6535
DOI:10.1002/cpt.160