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As mechanisms driving the lack of regeneration continue to be established, adjunctive pharmaceuticals to address the pathophysiology of the remaining muscle may offer partial remediation. Studies were designed to evaluate the tolerance and efficacy of two FDA\u2010approved pharmaceutical modalities to address the pathophysiology of the remaining muscle tissue after VML injury: (1) nintedanib (an anti\u2010fibrotic) and (2) combined formoterol and leucine (myogenic promoters). Tolerance was first established by testing low\u2010 and high\u2010dosage effects on uninjured skeletal muscle mass and myofiber cross\u2010sectional area in adult male C57BL\/6J mice. Next, tolerated doses of the two pharmaceutical modalities were tested in VML\u2010injured adult male C57BL\/6J mice after an 8\u2010week treatment period for their ability to modulate muscle strength and whole\u2010body metabolism. The most salient findings indicate that formoterol plus leucine mitigated the loss in muscle mass, myofiber number, whole\u2010body lipid oxidation, and muscle strength, and resulted in a higher whole\u2010body metabolic rate (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.016); nintedanib did not exacerbate or correct aspects of the muscle pathophysiology after VML. This supports ongoing optimization efforts, including scale\u2010up evaluations of formoterol treatment in large animal models of VML.<\/jats:p>","DOI":"10.14814\/phy2.15756","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T02:14:40Z","timestamp":1687140880000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exploring skeletal muscle tolerance and whole\u2010body metabolic effects of <scp>FDA<\/scp>\u2010approved drugs in a volumetric muscle loss model"],"prefix":"10.14814","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4156-4075","authenticated-orcid":false,"given":"Shefali R.","family":"Bijwadia","sequence":"first","affiliation":[{"name":"School of Kinesiology University of Minnesota  Minneapolis Minnesota 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