J vet Pharmacol Therap. 2020;00:1–11. wileyonlinelibrary.com/journal/jvp | 1 © 2020 John Wiley & Sons Ltd 1 | INTRODUCTION Increase in number of animal species, especially pet animals, is treated as family members and their owner demands same level of care as they expect for themselves. This revolution in attitude has made the scientists to pay more attention toward the development of more effective and innovative veterinary therapies (Johnson & Bruneau, 2019; Melson, 2019). Domestic cat (Felis catus) is worldwide popular pet and its clinical and pharmacological studies have not been under- taken as frequently as in other animal species and clinicians extrapo- late the data from other animal species or human but pharmacological response could be different. Many drugs that are safe to use in ani- mals and human but they can be extremely toxic to cats (Kang, Ko, & Park, 2018; Krull, Thomovsky, Chen, Mealey, & Papich, 2019; Savides, Oehme, Nash, & Leipold, 1984; Zaka-Ur-Rehman & Rasheed, 2019). This difference is due to poor metabolic capability as cats lack methyla- tion and most importantly glucurono-conjugation processes. Poor syn- thesis of glucuronides is due to low availability of enzyme glucuronyl transferase (Shrestha et al., 2011; Toutain, Ferran, & Bousquet-Mélou, 2010). Consequently, this leads to slow clearance and enhanced ad- verse effects of drug. Due to difference in metabolic capacity with respect to other species, a narrow spectrum of drug choices remains Received: 13 June 2019 | Revised: 19 October 2019 | Accepted: 30 October 2019 DOI: 10.1111/jvp.12836 PHARMACOKINETIC REPORT Disposition of cyadox in domesticated cats following oral, intramuscular, and intravenous administration Adeel Sattar 1,2 | Mian Abdul Hafeez 3 | Qin Wu 1,4 | Adnan Hassan Tahir 5 | Muhammad Abu Bakr Shabbir 6 | Dongmei Chen 1 | Lingli Huang 1 | Shuyu Xie 1 | Zonghui Yuan 1,4 1 National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, China 2 Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan 3 Department of Parasitology, University of Veterinary and Animal Sciences, Lahore, Pakistan 4 MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China 5 College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China 6 Department of Microbiology, University of Veterinary and Animal Sciences, Lahore, Pakistan Correspondence Zonghui Yuan and Shuyu Xie, National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, Hubei 430070, China. Emails: yuan5802@mail.hzau.edu.cn (Z.Y.); snxsy1@126.com (S.X.) Funding information National Natural Science Foundation of China, Grant/Award Number: 31302140 Abstract Cyadox (CYX) is a synthetic antibacterial agent of quinoxaline with much lower toxic effects. A safety criterion of CYX for clinical use was established by studying the pharmacokinetics and metabolism of CYX after oral (PO), intramuscular (IM), and in- travenous (IV) administration. CYX was administered in six domesticated cats (three males and three females) by PO (40 mg/kg.b.w.), IM (10 mg/kg.b.w.), and IV (10 mg/ kg.b.w.) routes in a crossover pattern. Highly sensitive liquid chromatography with ultraviolet detection (HPLC-UV) method was developed for detection of CYX and its metabolites present in plasma, urine, and feces. The bioavailability of CYX after PO and IM routes was 4.37% and 84.4%. The area under curves (AUC), mean resident time (MRT), and clearance (CL) of CYX and its metabolites revealed that CYX quickly metabolized into its metabolites. The total recovery of CYX and its main metabo- lites was >60% after each route. PO delivery suggesting first pass effect in cats that might make this route suitable for intestinal infection and IM injection could be better choice for systemic infections. Less ability of glucuronidation did not show any im- pact on CYX metabolism. The findings of present study provide detailed information for evaluation of CYX. KEYWORDS cyadox, domesticated cats, metabolism, pharmacokinetics, UV-HPLC