Development and application of a physiologically based pharmacokinetic model for orbifloxacin in crucian carp (Carassius auratus)

Abstract

Crucian carp (Carassius auratus), with the characteristics of strong adaptability, excellent reproductive ability, and rich nutritional value, is an essential freshwater fish reared in China (Yang et al., 2020). The annual production of crucian carp in 2020 exceeded 2.75 million tons (FAO, 2020). With the rapid development of intensive aquaculture, however, fish are suffering from many pathogens, such as Aeromonas hydrophila (Shan et al., 2018; Zdanowicz et al., 2020), Rahnella aquatilis (Liang et al., 2020), and Edwardsiella ictalurid (Geng et al., 2013), which have caused substantial economic losses (Yang et al., 2022). To reduce these losses, treatment with effective antibacterial agents is necessary.Orbifloxacin is a fluoroquinolone antimicrobial labeled for cats, dogs, and horses . It inhibits DNA gyrase in bacteria to inhibit DNA and RNA synthesis. Although unapproved in aquaculture in China, orbifloxacin is an effective alternative to treat diseases in fish. Previous studies have indicated

A physiologically based pharmacokinetic/pharmacodynamic model to determine dosage regimens and withdrawal intervals of aditoprim against Streptococcus suis

“…The determination coefficient ( R 2 ) values were derived from regression analysis, and the model simulation was acceptable if the value of R 2 was equal to or higher than 0.75 ( Lin et al, 2017 ). The performance of the PBPK model was assessed by the mean absolute percentage error (MAPE) value, which was less than 50% and considered an acceptable prediction ( Yang et al, 2022 ).…”

Development and Application of a Physiologically Based Pharmacokinetic Model for Diclazuril in Broiler Chickens

“…7 This value was calculated as 1 − (0.5712 + 0.2678 + 0.0064 + 0.0214 + 0.0071 + 0.0322 + 0.0161). 8 This value was calculated as 1 − (0.0764 + 0.2505 + 0.2012 + 0.2526).…”

“…According to our previous reports [8,27], a local sensitivity analysis was performed to determine which parameters had the most influence on the diclazuril concentrations in muscle, and the normalized sensitivity coefficient (NSC) values were calculated for each parameter [27]. A parameter was considered significant during postexposure if its NSC exceeded an absolute value of 0.25 [28].…”

“…In recent years, physiologically based pharmacokinetic (PBPK) models have emerged as a reliable tool for forecasting veterinary drug residues in animal-derived foods such as meat [8][9][10], milk [11][12][13], and eggs [14][15][16]. Compared to traditional post-slaughter monitoring methods, PBPK models are predictive and work based on mass-balance equations that are defined by physiological mechanisms [8]. Previous PBPK models in chickens were mostly developed for antibacterial drugs [10,17], with only one model available for the more widely used coccidiostats (monensin) [18].…”