title: Pharmacokinetics and Metabolism of Cyadox and Its Main Metabolites in Beagle Dogs Following Oral, Intramuscular, and Intravenous Administration.
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.
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors.forename: Adeel
authors.initials: A
authors.lastname: Sattar
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Xie
authors.affiliation: 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.
authors.forename: Lingli
authors.initials: L
authors.lastname: Huang
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University Wuhan, China.
authors.forename: Zahid
authors.initials: Z
authors.lastname: Iqbal
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University Wuhan, China.
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Shabbir
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors.forename: Yuanhu
authors.initials: Y
authors.lastname: Pan
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University Wuhan, China.
authors.forename: Hafiz I
authors.initials: HI
authors.lastname: Hussain
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Chen
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Tao
authors.affiliation: MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors.forename: Mujahid
authors.initials: M
authors.lastname: Iqbal
authors.affiliation: 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.
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Yuan
keywords: beagle dogs; cyadox; metabolism; metabolites; pharmacokinetics