Creatine lysinate – part I: investigation of the toxicity and the influence on some biochemical parameters in mice Ivanka Kostadinova 1 , Nikolai Danchev 1 , Boycho Landzhov 2 , Lyubomir Marinov 1 , Ivalina Ivanova 1 , Dobrina Tsvetkova 3 1 Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria 2 Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical University of Sofia, Sofia, Bulgaria 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria Corresponding author: Ivanka Kostadinova (i.kostadinova@pharmfac.mu-sofia.bg) Received 12 July 2023  ♦  Accepted 27 August 2023  ♦  Published 28 September 2023 Citation: Kostadinova I, Danchev N, Landzhov B, Marinov L, Ivanova I, Tsvetkova D (2023) Creatine lysinate – part I: investigation of the toxicity and the influence on some biochemical parameters in mice. Pharmacia 70(4): 895–899. https://doi.org/10.3897/phar- macia.70.e109446 Abstract In our study we investigated the acute toxicity of а newly synthesized creatine lysinate as well as its effect on the biochemical pa- rameters in mice. Creatine lysinate exerts better solubility in water (3.3%) in comparison to creatine monohydrate (1.4%) at 20 °C and it is determined as a non-toxic aſter intraperitoneal (LD50 – 4543 mg/kg) and oral administration (LD50 > 8000 mg/kg). Oral administration of creatine lysinate at doses of 3 g/kg/day and 6 g/kg/day for 2 weeks reduced the creatine kinase levels, which indi- cates muscle protection. An increased levels of liver enzymes like alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) was observed aſter the supplementation with creatine lysinate at both administered doses and the level of lactate was com- parable both in the studied and the control group. Keywords Biochemistry, creatine derivatives, mice, LD50 Introduction Creatine deserves a special place among ergogenic sup- plements, as it is one of the most studied and scientifi- cally supported supplements on the market. Creatine is a naturally occurring non-protein nitrogen compound synthesized in the liver and kidney from amino acids ar- ginine, glycine and methionine (Ribeiro et al. 2021). e storage of creatine occurs mainly in skeletal muscle, cor- responding to 95%, where it remains as a free (40%) or a phosphorylated creatine (60%). Creatine is also found in the brain, liver, kidneys and testicles (Persky and Brazeau 2001; Mendes and Tirapegui 2002). In addition to creatine synthesis in the body, the food provide about 1 gram of creatine/day, mainly through the consumption of ani- mal products, such as beef and fish (Greenhaf et al. 1994; Engelhardt et al. 1998). e average daily requirement is 2 grams/day: 1 gram from endogenous production and 1 gram obtained from the diet (Maughan et al. 2004; Calfee and Fadale 2006; Alves and Lima 2009). Creatine mono- hydrate (CrM) is considered as a standard for comparison to other creatine derivatives because of its well-known Copyright Kostadinova I et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Pharmacia 70(4): 895–899 DOI 10.3897/pharmacia.70.e109446 Research Article