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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]


Efaproxiral (INN) is an analogue of the cholesterol drug bezafibrate developed for the treatment of depression, traumatic brain injury, ischemia, stroke, myocardial infarction, diabetes, hypoxia, sickle cell disease, hypercholesterolemia and as a radio sensitiser.[1][2][3] The chemical is a propanoic acid in the class of amphipathic carboxylic acids. Most propanoic acid produced is consumed as a preservative for both animal feed and food for human consumption. One use for efaproxiral is to increase the efficacy of certain chemotherapy drugs which have reduced efficacy against hypoxic tumours, and can thus be made more effective by increased offloading of oxygen into the tumour tissues.[4][5][6] No benefit was seen for efaproxiral in phase III clinical trials.[7] The increased oxygenation of tissues could theoretically also produce enhanced exercise capacity in feline, rat and canine models for approximately 100 min. immediately after a high dosage 45 min. intravenous infusion.[8] This has led World Anti-Doping Agency to categorise efaproxiral under a prohibited method to artificially enhance the uptake, transport or delivery of oxygen.[9] There is no existing evidence that efaproxiral can effectively enhance performance in humans.[10] Efaproxiral can be absorbed via transdermal, rectal, inhalation and gastrointestinal routes, though not at plasma concentrations great enough to alter the oxygen-haemoglobin dissociation curve.[11] Efaproxiral is explicitly excluded from the 2012 World Anti-Doping Agency list of Prohibited Substances and is explicitly included in the Prohibited Methods section M1 as a forbidden procedure to alter the oxygen-haemoglobin dissociation curve in order to allosterically modify haemoglobin.[12]


  1. Farace, Melikyan (2008). "Cognitive Dysfunction, Mood Disorders, and Fatigue". CANCER NEUROLOGY IN CLINICAL PRACTICE: 242–248. doi:10.1007/978-1-59745-412-4_7.
  2. [1]
  3. Kunert MP, Liard JF, Abraham DJ (August 1996). "RSR-13, an allosteric effector of haemoglobin, increases systemic and iliac vascular resistance in rats". Am. J. Physiol. 271 (2 Pt 2): H602–13. PMID 8770102.
  4. Donnelly ET, Liu Y, Rockwell S (March 2006). "Efaproxiral (RSR13) plus oxygen breathing increases the therapeutic ratio of carboplatin in EMT6 mouse mammary tumors". Exp. Biol. Med. (Maywood). 231 (3): 317–21. PMID 16514179.
  5. Engel RH, Kaklamani VG (April 2006). "Role of efaproxiral in metastatic brain tumours". Expert Rev Anticancer Ther. 6 (4): 477–85. doi:10.1586/14737140.6.4.477. PMID 16613536.
  6. Scott C, Suh J, Stea B, Nabid A, Hackman J (December 2007). landingpage.htm?issn=0277-3732&volume=30&issue=6&spage=580 "Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases" Check |url= value (help). Am. J. Clin. Oncol. 30 (6): 580–7. doi:10.1097/COC.0b013e3180653c0d. PMID 18091051.
  7. [2]
  8. Watanabe T; Takeda T; Omiya S; et al. (August 2008). "Reduction in hemoglobin-oxygen affinity results in the improvement of exercise capacity in mice with chronic heart failure". J. Am. Coll. Cardiol. 52 (9): 779–86. doi:10.1016/j.jacc.2008.06.003. PMID 18718428. Unknown parameter |author-separator= ignored (help)
  9. WADA 2009 Prohibited List
  10. Antonio Claudio Lucas da Nobrega (Feb 2002). "RSR13 and allosteric change in the hemoglobin-oxygen Afinity". Journal of Sports Medicine. 8. ISSN 1517-8692.
  11. Campanini, Bruno, Raboni, Mozzarelli (January 2003). "Oxygen Delivery by Allosteric Effectors of Hemoglobin, Blood Substitutes, and Plasma Expanders". Burger's Medicinal Chemistry, Drug Discovery and Development. doi:10.1002/0471266949.bmc048.
  12. http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/2012/WADA_Prohibited_List_2012_EN.pdf