Features of the body distribution of ceftriaxone in warm-blooded animals

DOI: https://doi.org/10.29296/25419218-2020-06-09
Issue: 
6
Year: 
2020

A.A. Bez’yazychnaya, V.K. Shormanov, L.E. Siplivaya, B.M. Tagirmirzoev, M.V. Rymarova, I.M. Zhukov Kursk State Medical University, 3, Karl Marx St., Kursk 305004, Russian Federation

Introduction. Ceftriaxone is a yellowish-white crystalline powder, is hygroscopic and readily soluble in water. It is a third-generation antibiotic with a broad spectrum of action. Objective: to study of the body distribution of ceftriaxone in warm-blooded animals when it is given at lethal doses. Material and methods. The distribution of the substance in free form or included in the erythrocyte carriers was studied in the groups of healthy mice and those with simulated toxic kidney damage caused by HgCl2. Isolation was carried out with an acetone-water mixture of 5:5 at a mass ratio of the insulating mixture and the biological object (2:1). The investigators used thin-layer chromatography, ultraviolet spectrophotometry, and high performance liquid chromatography for the identification of ceftriaxone and UV spectrophotometry for its quantitative determination. Results. Ceftriaxone was found in large quantities in the visceral organs and blood of poisonous organisms. Ceftriaxone intravenously injected in free form to healthy animals was present in the highest amounts in the bladder with urine (2718.93 mg/100 g), whereas it was also seen in the blood (523.02 mg/100 mg) and urinary bladder (571.10 mg/100 mg) of animals with simulated toxic kidney damage caused by HgCl2. When ceftriaxone included into the erythrocyte carriers was intravenously injected to the healthy mice, the maximum concentration of the drug was observed in the blood (937.57 mg/100 g) and urinary bladder (1184.59 mg/100 g). When erythrocyte carriers with ceftriaxone were administered to the group of mice with simulated renal toxicity induced by HgCl2, there were changes in the distribution of the test antibiotic. The peak concentration was observed in the kidneys (668.61 mg/100 g) and blood (663.41 mg/100 g). Conclusion. The results of the investigations make it possible to imagine differences in the nature of ceftriaxone distribution in the warm-blooded animals in health and in simulated renal disease when the antibiotic was intravenously injected as a substance or part of erythrocyte carriers.

Keywords: 
ceftriaxone
erythrocyte carriers
mercury dichloride
distribution
isolation
purification
identification and determination

References: 
  1. Atinoz S., Ozer D., Ozer A., Temized A. Determination of ceftriaxone in aqueous humor and serum samples by differentialpulse adsorptive stripping voltammetry. Analyst. 1994; 6: 1575–7.
  2. Fli S.M., Elbashir A., Hassan Y. Spectroscopic methods for analysis of cephalosporins in pharmaceutical formulations. World J. of Analytical Chemistry. 2015; 3 (1A): 21–32. https://doi.org/10.12691/wjac-3-1A-5
  3. Provotorov V.M., Ivanova G.A. Rol' i mesto eritrotsitov v sisteme napravlennogo transporta razlichnyh farmakologicheskih sredstv. Klinicheskaja meditsina. 2009; 9: 4–8. [Provotorov V.M., Ivanova G.A. The role and place of erythrocytes in the directional transport system of various pharmacological agents. Klinicheskaya meditsina. 2009; 9: 4–8 (in Russian)]
  4. Shormanov V.K., Pravdjuk M.F. Dokazatel'stvo otravlenija tsiklopentolatom, vvedennym v zheludok teplokrovnyh, na osnove obnaruzhenija v organizmah ishodnogo otravljajuschego agenta i produkta ego transformatsii. Kurskij nauchno-prakticheskij vestnik «Chelovek i ego zdorov'e». 2016; 4: 100–6. https://doi.org/10.21626/vestnik/2016-4/17 [Shormanov V.K., Pravdyuk M.F. Proof of poisoning with cyclopentolate introduced into the stomach warm-blooded, based on the discovery in the organisms of the original poison agent and the product of its transformation. Kurskij nauchno-prakticheskij vestnik «Chelovek i ego zdorov'e». 2016; 4: 100–6. https://doi.org/10.21626/vestnik/2016-4/17 (in Russian)]
  5. Lindenmann J., Kugler S.A., Matzi V. et al. High extracellular levels of cefpirome in unaffected and infected lung tissue of patients. Antimicrob. Chemother. 2011; 66 (1): 160–4. https://doi.org/10.1093/jac/dkq413
  6. Nishino I., Fujitomo H., Umeda T. Determination of a new oral cephalosporin, cefmatilen hydrochloride hydrate, and its seven metabolites in human and animal high-performance liquid chromatography. J. of Chromatography. 2000; 749: 101–10.
  7. El-Shaboury S.R., Saleh G.A., Mohamed F.A., Rageh A.H. Analysis of cephalosporin antibiotics. J. of Pharmaceutical and Biomedical Analysis. 2007; 45 (1): 1–19. https://doi.org/10.1016/j.jpba.2007.06.002
  8. Shormanov V.K., Ostanin M.A., Astashkina A.P. Osobennosti raspredelenija 4-metoksigidroksibenzola v organizme teplokrovnyh zhivotnyh (krysy) pri letal'nyh otravlenijah. Sudebno-meditsinskaja ekspertiza. 2016; 59 (4): 48–53. https://doi.org/10.17116/sudmed201659448-53 [Shormanov V.K., Ostanin M.A., Astashkin A.P. Peculiarities of the distribution of 4-methoxyhydroxybenzene in the body of warm-blooded animals (rats) in case of lethal poisoning. Sudebno-medicinskaya ehkspertiza. 2016; 59 (4): 48–53. https://doi.org/10.17116/sudmed201659448-53. (in Russian)]
  9. Solangi A.R., Memon S.Q., Khuhawar M.Y., Bhanger M.I. Quantitative analysis of eight cephalosporin antibiotics in pharmaceutical products and urine by capillary zone electrophoresis. Acta Chromatographica, 2007; 19: 81–96.
  10. Hancu G., Sasebeşi A., Rusu A. et al. Study of the Electrophoretic Behavior of Cephalosporins by Capillary Zone Electrophoresis. Adv. Pharm. Bull. 2015; 5 (2): 223–9. https://doi.org/10.15171/apb.2015.031
  11. Rathinavel G., Mukherjee P.B., Valarmathy J. et al. Validated RP-HPLC method for simultaneous estimation evaluation of cefixime and cloxacillin in tablets. E-Journal of Chemistry. 2008; 5 (3): 648–51.
  12. Signs S.A., File T.M., Tan J.S. High-pressure liquid chromatographic method for analysis of cephalosporins. Antimicrobial Agents and Chemotherapy. 1984; 26 (5): 652–5.
  13. Johnson V.M., Allanson J.P., Causon R.C. Determination of the cephalosporin antibiotic cephradine in human plasma by high-performance liquid chromatography with ultraviolet detection. J. of Chromatography. 2000; 740 (1): 71–80.
  14. Zendelovska D., Stafilov T., Petrov S. Simultaneous quantification of cefaclor and cephalexine in blood plasma using high-performance liquid chromatography with UV detection. Acta Pharm. 2002; 52: 243–50.
  15. Shormanov V.K., Belyh E.A., Baranov Ju.N., Terskih A.P. Osobennosti raspredelenija bankola v organizme teplokrovnyh zhivotnyh. Sudebno-meditsinskaja ekspertiza. 2013; 56 (5): 34–7. [Shormanov V.K., Belykh E.A., Baranov Yu.N., Terskih A.P. Features of the distribution of bancol in the body of warm-blooded animals. Sudebno-medicinskaya ehkspertiza. 2013; 56 (5): 34–7 (in Russian)]