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Pharmacokinetics and Biodistribution of Rhopalurus junceus Scorpion Venom in Tumor-Bearing Mice after Intravenous and Oral Administration
Alexis Díaz-García * , Gilmara Pimentel González , Tais Basaco Bernabeu , Juan C. Rodríguez Aurrecochea , Hermis Rodríguez Sánchez , Iraida Sánchez Monzón , Maikel Hernández Gómez , Caridad Rodríguez Torres , Maria Regla Rodríguez Capote , Irania Guevara Orellanes
Abstract:  
Introduction: Rhopalurus junceus scorpion venom has shown potential for anticancer treatment. However, there are no scientific evidence about venom pharmacokinetic (PK) and biodistribution (BD) in tumor-bearing mice. Methods: 131I-labeled venom was administrated by intravenous (IV) and oral (PO) routes at the single dose of 12.5 mg/kg. Mice were sacrificed and blood samples, major organs, and tumor were taken at 10, 20, 40, 90, 180, 300, 480, and 1440 min. Results: For IV route, maximum peak concentration (Cmax), elimination half-lives, total body clearance (CL), distribution volume (Vd), mean residence time (MRT), and area under curve (AUC) were 21.77 ± 2.45 %Dosis·h/mL, 12.65 ± 2.1 h, 4.59 ± 0.23 mL/h, 83.80 ± 12 mL, 12.49 ± 2.71 h, and 21.77 ± 2.45 %Dosis·h/mL, respectively. For  PO route, they were 0.60 ± 0.07 %Dosis·h/mL, 9.33 ± 1.35 h, 36.94 ± 4.01 mL/h, 497.33 ± 30 mL, 12.40 ± 1.87 h, and 6.89 ± 1.18 %Dosis·h/mL, respectively. PK parameters (Cmax, CL, Vd, and AUC) showed significant differences between IV and PO routes. Bioavailability was 31.6 ± 4% for PO dose. Kidney, stomach, liver, and lung for IV and stomach, kidney, spleen, and lung for PO routes showed the major uptakes for 131I-labeled venom. In tumor tissue, after the maximum uptake for both routes, there was a consistent behavior of radioactivity respect to the major organs during the first 480 min. Conclusion: The PK and BD of R. junceus venom in mice depend on the administration route. These data represent a starting point for future experiments with this scorpion venom in experimental models of cancer.
Keywords: Intravenous, Mice, Oral administration, Radioactivity, Scorpion venom
Full-Text [PDF 734 kb]      
Type of Study: Full Length | Subject: Related Fields
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