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Modeling for Accelerated Discovery in Biology

Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion.

Journal article

Michael R Fettiplace, K. Lis, Richard Ripper, K. Kowal, A. Pichurko, D. Vitello, I. Rubinstein, David E. Schwartz, B. Akpa, G. Weinberg
Journal of Controlled Release, 2015
Semantic Scholar DOI PubMed
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APA   Click to copy
Fettiplace, M. R., Lis, K., Ripper, R., Kowal, K., Pichurko, A., Vitello, D., … Weinberg, G. (2015). Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion. Journal of Controlled Release.

Chicago/Turabian   Click to copy
Fettiplace, Michael R, K. Lis, Richard Ripper, K. Kowal, A. Pichurko, D. Vitello, I. Rubinstein, David E. Schwartz, B. Akpa, and G. Weinberg. “Multi-Modal Contributions to Detoxification of Acute Pharmacotoxicity by a Triglyceride Micro-Emulsion.” Journal of Controlled Release (2015).

MLA   Click to copy
Fettiplace, Michael R., et al. “Multi-Modal Contributions to Detoxification of Acute Pharmacotoxicity by a Triglyceride Micro-Emulsion.” Journal of Controlled Release, 2015.

BibTeX   Click to copy 

@article{michael2015a,
  title = {Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion.},
  year = {2015},
  journal = {Journal of Controlled Release},
  author = {Fettiplace, Michael R and Lis, K. and Ripper, Richard and Kowal, K. and Pichurko, A. and Vitello, D. and Rubinstein, I. and Schwartz, David E. and Akpa, B. and Weinberg, G.}
}

Abstract

Triglyceride micro-emulsions such as Intralipid® have been used to reverse cardiac toxicity induced by a number of drugs but reservations about their broad-spectrum applicability remain because of the poorly understood mechanism of action. Herein we report an integrated mechanism of reversal of bupivacaine toxicity that includes both transient drug scavenging and a cardiotonic effect that couple to accelerate movement of the toxin away from sites of toxicity. We thus propose a multi-modal therapeutic paradigm for colloidal bio-detoxification whereby a micro-emulsion both improves cardiac output and rapidly ferries the drug away from organs subject to toxicity. In vivo and in silico models of toxicity were combined to test the contribution of individual mechanisms and reveal the multi-modal role played by the cardiotonic and scavenging actions of the triglyceride suspension. These results suggest a method to predict which drug toxicities are most amenable to treatment and inform the design of next-generation therapeutics for drug overdose.

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