Predicting the Effective Dose of 5-Aminolevulinic Acid to Protect Humans From Renal Ischemia-Reperfusion Injury: A Study in Micro Miniature Pigs

Background: In rodent models, 5-aminolevulinic acid (5-ALA) was shown to prevent renal ischemia-reperfusion injury, but the data did not allow estimation of human equivalent dose (HED). Therefore, this study evaluated effects 5-ALA and estimated HED in micro miniature pigs, which have a metabolism closer that humans. Methods: We analyzed efficacy pharmacokinetics by administering it nine pigs 2 days before injury. A pathological score calculated on basis tissue damage; blood concentration required damage from expected back-calculating obtained approximate expression. The phase 1 trials (5-ALA vs. curve) were used calculate HED. Results: Dose-dependent improvement (rated as score) confirmed 7 after reperfusion. each animal, concentrations correlated with score. doses approximately 1.6 mg/kg 13.4 would be obtain histopathology scores 4 3.7 humans, respectively. Conclusions: This is first show can pigs. J Curr Surg. 2021;11(1):8-14 doi: https://doi.org/10.14740/jcs429