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Mitochondria as targets of drug toxicity: Lessons from the R118 phase I experience
Author(s) -
Brass EP,
Hoppel CL
Publication year - 2015
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.160
Subject(s) - ampk , adverse effect , activator (genetics) , mitochondrion , drug , pharmacology , toxicity , medicine , mechanism (biology) , mitochondrial toxicity , protein kinase a , kinase , biology , biochemistry , receptor , philosophy , epistemology
Solely the dose determines that a thing is not a poison . —Paracelsus 1493–1541 1 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.