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Sattar A, Xie S, Huang L, et al. Pharmacokinetics and Metabolism of Cyadox and Its Main Metabolites in Beagle Dogs Following Oral, Intramuscular, and Intravenous Administration. Front Pharmacol. 2016;7:236doi: 10.3389/fphar.2016.00236.
Sattar, A., Xie, S., Huang, L., Iqbal, Z., Qu, W., Shabbir, M. A., Pan, Y., Hussain, H. I., Chen, D., Tao, Y., Liu, Z., Iqbal, M., & Yuan, Z. (2016). Pharmacokinetics and Metabolism of Cyadox and Its Main Metabolites in Beagle Dogs Following Oral, Intramuscular, and Intravenous Administration. Frontiers in pharmacology, 7236. https://doi.org/10.3389/fphar.2016.00236
Sattar, Adeel, et al. "Pharmacokinetics and Metabolism of Cyadox and Its Main Metabolites in Beagle Dogs Following Oral, Intramuscular, and Intravenous Administration." Frontiers in pharmacology vol. 7 (2016): 236. doi: https://doi.org/10.3389/fphar.2016.00236
Sattar A, Xie S, Huang L, Iqbal Z, Qu W, Shabbir MA, Pan Y, Hussain HI, Chen D, Tao Y, Liu Z, Iqbal M, Yuan Z. Pharmacokinetics and Metabolism of Cyadox and Its Main Metabolites in Beagle Dogs Following Oral, Intramuscular, and Intravenous Administration. Front Pharmacol. 2016 Aug 03;7:236. doi: 10.3389/fphar.2016.00236. eCollection 2016. PMID: 27536243; PMCID: PMC4971586.
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Front Pharmacol. 2016 Aug 03;7:236. doi: 10.3389/fphar.2016.00236. eCollection 2016.

Pharmacokinetics and Metabolism of Cyadox and Its Main Metabolites in Beagle Dogs Following Oral, Intramuscular, and Intravenous Administration.

Frontiers in pharmacology

Adeel Sattar, Shuyu Xie, Lingli Huang, Zahid Iqbal, Wei Qu, Muhammad A Shabbir, Yuanhu Pan, Hafiz I Hussain, Dongmei Chen, Yanfei Tao, Zhenli Liu, Mujahid Iqbal, Zonghui Yuan

Affiliations

  1. National Reference Laboratory of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
  2. National Reference Laboratory of Veterinary Drug Residues, Huazhong Agricultural UniversityWuhan, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural UniversityWuhan, China.
  3. MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University Wuhan, China.
  4. MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
  5. National Reference Laboratory of Veterinary Drug Residues, Huazhong Agricultural UniversityWuhan, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural UniversityWuhan, China; MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural UniversityWuhan, China.

PMID: 27536243 PMCID: PMC4971586 DOI: 10.3389/fphar.2016.00236

Abstract

Cyadox (Cyx) is an antibacterial drug of the quinoxaline group that exerts markedly lower toxicity in animals, compared to its congeners. Here, the pharmacokinetics and metabolism of Cyx after oral (PO), intramuscular (IM), and intravenous (IV) routes of administration were studied to establish safety criteria for the clinical use of Cyx in animals. Six beagle dogs (3 males, 3 females) were administered Cyx through PO (40 mg kg(-1) b.w.), IM (10 mg kg(-1) b.w.), and IV (10 mg kg(-1) b.w.) routes with a washout period of 2 weeks in a crossover design. Highly sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV) was employed for determination of Cyx and its main metabolites, 1, 4-bisdesoxycyadox (Cy1), cyadox-1-monoxide (Cy2), N-(quinoxaline-2-methyl)-cyanide acetyl hydrazine (Cy4), and quinoxaline-2-carboxylic acid (Cy6) in plasma, urine and feces of dogs. The oral bioavailability of Cyx was 4.75%, suggesting first-pass effect in dogs. The concentration vs. time profile in plasma after PO administration indicates that Cyx is rapidly dissociated into its metabolites and eliminated from plasma earlier, compared to its metabolites. The areas under the curve (AUC) of Cyx after PO, IM and IV administration were 1.22 h × μg mL(-1), 6.3 h × μg mL(-1), and 6.66 h × μg mL(-1), while mean resident times (MRT) were 7.32, 3.58 and 0.556 h, respectively. Total recovery of Cyx and its metabolites was >60% with each administration route. In feces, 48.83% drug was recovered after PO administration, while 18.15% and 17.11% after IM and IV injections, respectively, suggesting renal clearance as the major route of excretion with IM and IV administration and feces as the major route with PO delivery. Our comprehensive evaluation of Cyx has uncovered detailed information that should facilitate its judicious use in animals by improving understanding of its pharmacology.

Keywords: beagle dogs; cyadox; metabolism; metabolites; pharmacokinetics

References

  1. Res Vet Sci. 2012 Dec;93(3):1380-6 - PubMed
  2. J Pharm Sci. 2015 Jan;104(1):233-43 - PubMed
  3. Trends Mol Med. 2011 Jul;17(7):380-8 - PubMed
  4. Nat Biotechnol. 2006 Sep;24(9):1065-6 - PubMed
  5. J Am Vet Med Assoc. 1997 Jan 1;210(1):55-8 - PubMed
  6. Vet J. 2009 Jan;179(1):25-37 - PubMed
  7. J Agric Food Chem. 2013 Oct 2;61(39):9510-5 - PubMed
  8. Infect Immun. 2004 Jun;72(6):3252-9 - PubMed
  9. Food Chem Toxicol. 2006 Jan;44(1):36-41 - PubMed
  10. J Pharmacokinet Biopharm. 1978 Dec;6(6):547-58 - PubMed
  11. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Oct 15;874(1-2):7-14 - PubMed
  12. Rapid Commun Mass Spectrom. 2009 Jul;23(13):2026-34 - PubMed
  13. J Proteomics. 2015 Sep 8;127(Pt B):365-76 - PubMed
  14. Talanta. 1988 Oct;35(10):816-8 - PubMed
  15. ILAR J. 2014;55(1):100-18 - PubMed
  16. J Infect Dis. 1975 Apr;131(4):367-75 - PubMed
  17. J Anim Sci. 2006 Sep;84(9):2367-73 - PubMed
  18. Food Chem Toxicol. 2015 Oct;84:115-24 - PubMed
  19. J Pharm Pharmacol. 1978 Aug;30(8):476-8 - PubMed
  20. Drug Metab Dispos. 1995 Oct;23(10):1008-21 - PubMed
  21. Xenobiotica. 2011 Nov;41(11):964-71 - PubMed
  22. Pharmacol Rev. 1997 Dec;49(4):403-49 - PubMed
  23. Pharm Res. 2000 Feb;17(2):135-40 - PubMed
  24. J Anim Physiol Anim Nutr (Berl). 2006 Jun;90(5-6):238-43 - PubMed
  25. Chem Res Toxicol. 2015 Mar 16;28(3):470-81 - PubMed
  26. J Pharm Sci. 1982 Mar;71(3):372-3 - PubMed
  27. Anal Sci. 2005 Dec;21(12):1495-9 - PubMed
  28. Regul Toxicol Pharmacol. 2015 Nov;73(2):652-9 - PubMed
  29. Drug Metab Dispos. 2009 May;37(5):1056-64 - PubMed
  30. J Agric Food Chem. 2015 Jun 10;63(22):5557-69 - PubMed
  31. BMC Vet Res. 2015 Sep 17;11:239 - PubMed
  32. Drug Metab Rev. 1991;23(3-4):355-73 - PubMed
  33. Res Vet Sci. 2012 Aug;93(1):374-7 - PubMed
  34. Front Pharmacol. 2016 Mar 21;7:64 - PubMed
  35. Rapid Commun Mass Spectrom. 2011 Aug 30;25(16):2333-44 - PubMed

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