Pharmacokinetics of two dosing forms of a recrystallized enrofloxacin as hydrochloride dihydrate in tilapia (Oreochromis niloticus × Oreochromis mossambicus)
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A recrystallized solvate of enrofloxacin in the form of hydrochloride dihydrate (enro-C) has shown a greater bioavailability in other species and a higher solubility in water compared to standard enrofloxacin. This led to define the pharmacokinetics (PK) of enro-C in tilapia (Oreochromis niloticus × Oreochromis mossambicus), when administered as in-feed medication, either by the addition of enro-C during food pelleting (T2) or by the coating of pre-manufactured pellets with a gelatin suspension containing enro-C (T1). T1 and T2 were both prepared with 3000 mg of enro-C/kg of feed, and a total dose of 10 mg/kg based on feed consumption. The trial was carried out in fresh water tanks, collecting blood samples twelve times during 70 h (three repetitions with five tilapias per sampling time). Maximum plasma concentrations (CMAX) for T1 and T2 were 1.35 ± 0.55 μg/mL and 1.92 ± 0.26 μg/mL, respectively. The time to achieve CMAX (TMAX) occurred almost simultaneously at 6.5 h. The area under the plasma vs time concentrations (AUC0-24) were 25.41 ± 24 μg/mL/h and 57.91 ± 30 μg/mL/h for T1 and T2, respectively. MIC data from available literature indicate that PK/PD ratios (CMAX/MIC90 and AUC0-24/MIC90) are higher in T2 compared to T1 in tilapia. Results indicate that the customary dose of enrofloxacin (10 mg/kg) using enro-C reaches, in particular, higher values of CMAX and AUC0-24. Thus, based on these results, it is feasible to propose enro-C for the treatment of bacterial diseases in tilapia, preferably as was done in T2. However, before this happens, toxicity and drug-residue studies, as well as environmental and public health issues, must be resolved.
KeywordsTilapia Enrofloxacin Enro-C Pharmacokinetics PK/PD ratios
The authors are grateful for the skillful definition of the new crystal form of enrofloxacin (enro-C) carried out at The School of Chemistry, Trinity College; Dublin, Republic of Ireland.
This project was partially supported by CONACyT, project No. 203.
Compliance with ethical standards
Conflict of interest
Authors have no conflict of interests. The National Autonomous University of Mexico (UNAM), owner of the patent, is open to licensing of enro-C.
All applicable international, national, and institutional guidelines for the care and use of animals were followed by the authors.
- Alderman DJ, Hastings TS (1998) Antibiotic use in aquaculture: development of antibiotic resistance – potential for consumer health risks. Int J Food Sci Technol 33:139–155. https://doi.org/10.1046/j.1365-2621.1998.3320139.x CrossRefGoogle Scholar
- Austin B, Austin DA (2007) Bacterial fish pathogens. Disease of farmed and wild fish. Dobbins P, Ed. (4th ed.). Springer, ChichesterGoogle Scholar
- Bennett JV, Brodie JL, Benner EJ, Kirby WM (1966) Simplified, accurate method for antibiotic assay of clinical specimens. Appl Microbiol 14(2) 170–177 Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/4959982%5Cn http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC546645. Accessed Oct 2018
- Bowser PR, Babish JG (1991) Clinical pharmacology and efficacy of fluoroquinolones in fish. Annual Review of Fish Diseases, 1(C), 63–66. https://doi.org/10.1016/0959-8030(91)90022-C
- Chien Y 2009 “Novel Drug Delivery Systems.” In J Neurosci Nurs, edited by James Swarbrick, 2nd ed., 14:139–96. Chapel Hill, North Carlina. https://doi.org/10.1097/JNN.0b013e318193458b
- El-Sayed, AFM (2006) Tilapia culture. Wallingford, Oxfordshire. https://doi.org/10.1079/9780851990149.0000
- Fais AP, Scrapino R, Blado AF et al (2017) LC-MS/MS methods for sulfadimethoxine and ormetoprim analysis in feed and fish fillet and a leaching study for feed after alternative procedures for the incorporation of drugs. Food Addit Contam B 34(4):501–508. https://doi.org/10.1080/19440049.2016.1267875 CrossRefGoogle Scholar
- FAO (2016) The State of World Fisheries and Aquaculture 2016. Contributing to food security and nutrition for all. Rome. http://www.fao.org/3/a-i5555e.pdf Cited 20 Jan 2017
- Inglis V, Richards RH (1991) The in vitro susceptibility of Aeromonas salmonicida and other fish pathogenic bacteria to 29 antimicrobial agents. J Fish Dis 14(6):641–650. https://doi.org/10.1111/j.1365-2761.1991.tb00622.x CrossRefGoogle Scholar
- Jimenez R (2007) Enfermedades de Tilapia en Cultivo (Tilapia disaeses in culture). GuayaquilGoogle Scholar
- Noga EJ. (2010) Fish disease: diagnosis and treatment, Second Edition. Ames, Iowa. https://doi.org/10.1002/9781118786758
- Oyebanji M, Omoregie E (2002) Oxytetracycline-induced blood disorder in juvenile Nile tilapia. J Worls Aquacult Soc 33(3):0–5. https://doi.org/10.1111/j.1749-7345.2002.tb00514.x Google Scholar
- Rey A, Iregui C, Verján N (2002) Diagnóstico clínico patológico de brotes de enfermedad en tilapia roja (Oreochromis spp). Pdf. Rev Med Vet Zoot 49(13–21):9Google Scholar
- SAGARPA (2017) Avanza México como una potencia en producción acuícola (Mexico advances as a power in aquaculture production) (Vol. BCS/135/20). Mexico City. Retrieved from https://www.gob.mx/sagarpa/prensa/avanza-mexico-como-una-potencia-en-produccion-acuicola Cited 20 Jan 2018. Accessed Oct 2018
- Soto-Rodríguez S, Armenta M, Gomez-Gil B (2006) Effects of enrofloxacin and florfenicol on survival and bacterial population in an experimental infection with luminescent Vibrio campbellii in shrimp larvae of Litopenaeus vannamei. Aquaculture 255(1–4):48–54. https://doi.org/10.1016/j.aquaculture.2005.11.035 CrossRefGoogle Scholar
- Udomkusonsri P, Arthitvong S, Klangkaew N et al (2007) Pharmacokinetics of enrofloxacin in Koi carp (Cyprinus carpio) after various routes of administration. Kasetsart J. (Nat. Sci.) 41:62–68Google Scholar
- United States Food and Drug Administration (2015) Freedom of information summary (Vol. 30). Silver Spring, Washington DC. Retrieved from https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/385 Cited 32 Jul 2018. Accessed Oct 2018
- Zaki MM, Eissa AE, Saeid S (2011) Assessment of the immune status in Nile tilapia (Oreochromis niloticus) experimentally challenged with toxogenic/septicemic bacteria during treatment trial with florfenicol andenrofloxacin. WJFMS 3(1): 21–36Google Scholar