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.
Highlights
Quinoxaline 1, 4-di-N-oxide (QdNO) derivatives are effective synthetic antibacterial agents used worldwide since 1970 to treat several gram-positive and gram-negative bacterial infections in animals (Wang et al, 2015a,b; Cheng et al, 2016)
In view of the physiological similarities of dogs with humans and other animals, the present study aimed to explore the metabolism and pharmacokinetic profiles of Cyx and its main metabolites (Cy1, Cy2, Cy4, and Cy6) in beagle dogs following oral (PO), intramuscular (IM), and intravenous (IV) administration using high-performance liquid chromatography with ultraviolet (HPLC-UV) detection
The correlation coefficient values of all five metabolites indicating functional linear relationship at different concentrations were >0.999 across the concentration ranges used for all samples
Summary
Quinoxaline 1, 4-di-N-oxide (QdNO) derivatives are effective synthetic antibacterial agents used worldwide since 1970 to treat several gram-positive and gram-negative bacterial infections in animals (Wang et al, 2015a,b; Cheng et al, 2016). Cyadox (Cyx), 2-formylquinoxaline-N1, N4-dioxide cyanocetylhydrazone, is a novel derivative of QdNO, and a promising antibacterial agent believed to be safer for use than its congeners (Fan et al, 2000; Fang et al, 2006; Wang et al, 2015c). It has been characterized as an effective broad-spectrum antibacterial agent against the majority of pathogenic bacteria (including Staphylococcus, Pasturella, and Salmonella spps) in animals (Fan et al, 2000; Huang et al, 2002; Wang et al, 2005). The findings to date support the efficacy of Cyx as a safe and effective quinoxalinebased antibacterial agent in different animal species, including canines
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
