In vivo assessment of mitochondrial toxicity.
Drug effects on mitochondrial function are frequently characterized in vitro. Whether these findings are relevant pharmacologically or toxicologically is generally unclear. Methods for in vivo assessment of mitochondrial function would help establish biological significance, but none is widely accepted or readily available. Ideally, these methods would be sensitive and specific, noninvasive, predictive of efficacy or toxicity, translatable from preclinical to clinical studies and localizable to the target organ. Although not fully developed or validated, several approaches to in vivo mitochondrial assessment show promise. Collaboration between scientists from academia, the pharmaceutical industry, and regulatory agencies will be required to develop and apply these methods.
Hamilton
Bradley F
BF
GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709-3398, USA. brad.f.hamilton@gsk.com
Stokes
Alan H
AH
Lyon
Jon
J
Adler
Rick R
RR
D000818:Animals; D015415:Biomarkers; D001826:Body Fluids / Q000737:chemistry / Q000378:metabolism; D001944:Breath Tests; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D049268:Positron-Emission Tomography
D015415:Biomarkers