title: Mitochondria as targets of drug toxicity: Lessons from the R118 phase I experience.
abstract: 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.
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Torrance, California, USA.
authors.forename: E P
authors.initials: EP
authors.lastname: Brass
authors.affiliation: Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Hoppel
mesh_terms: D016503:Drug Delivery Systems / Q000379:methods*; D015507:Drugs, Investigational / Q000008:administration & dosage* / Q000009:adverse effects*; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008297:Male
chemical_list: D015507:Drugs, Investigational; D042967:Electron Transport Complex I