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  • Pharmacokinetic evaluation ...
    Olivares-Hernández, Roberto; Riaño-Umbarila, Lidia; Becerril, Baltazar; Alagón, Alejandro; Vázquez-López, Hilda

    Toxicon, 05/2024, Letnik: 242
    Journal Article

    A key aspect during the development of antivenoms is the evaluation of the efficiency and security of the therapeutic molecules. In this work, we report the pharmacokinetic analysis of a neutralizing single chain antibody fragment named LR (scFv LR) where three sheep were used as a large animal model. The animals were injected through i.v. route with 2 mg of scFv LR. Blood samples were drawn every minute within the first 15 min, the sampling continues at 20, 25, 30, 45, 60, 90, 120 min, subsequently at 1-h intervals, 3, 4, 5, 6 h, two more samples at 9 and 12 h and, two more samples at 24 and 48 h and finally at one-day intervals during 4 days. scFv LR levels were measured from blood serum and urine samples by an ELISA. The pharmacokinetics of the experimental data was analyzed using the three-exponential kinetics. The value of the fast initial component (τ1=0.409±0.258min) indicated that the scFv is distributed rapidly into the tissues. The mean residence time, MRT, was 45 ± 0.51 min and the clearance (CL), 114.3 ± 14.3 mL/min. From urine samples it was possible to detect significant amounts of scFv LR, which is evidence of renal elimination. Display omitted •The first pharmacokinetics of scFv LR against scorpion toxins was performed in sheep.•Sheep is a good large animal model for the evaluations svFC LR as antivenom.•The pharmacokinetics analysis suggest that this antibody format could be better than F(ab')2 for scorpion sting treatment.•Fast elimination of scFv antibody format could represent a key element to fight against scorpion stings.•New scorpion antivenoms could be based on scFv antibody format.