A physiologically based pharmacokinetic model of doxycycline for predicting tissue residues and withdrawal intervals in grass carp (Ctenopharyngodon idella). (March 2020)

• Record Type: Journal Article
• Authors: Xu, Ning; Li, Miao; Chou, Wei-Chun; Lin, Zhoumeng
• Is Part Of: Food and chemical toxicology. Volume 137(2020)
• Publication Date: 2020-03
• Subjects: Doxycycline -- Physiologically based pharmacokinetic (PBPK) model -- Grass carp -- Drug residue -- Withdrawal time -- Food safety; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2020.111127
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: The extensive use of doxycycline in aquaculture results in drug residue violations that negatively impact human food safety. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model for doxycycline to predict drug residues and withdrawal times (WTs) in grass carp ( Ctenopharyngodon idella ) after daily oral administration for 3 days. Physiological parameters including cardiac output and organ weights were measured experimentally. Chemical-specific parameters were obtained from the literature or estimated by fitting to the observed data. The model properly captured the observed kinetic profiles of doxycycline in tissues (i.e., liver, kidney, muscle + skin and gill). The predicted WT in muscle + skin by Monte Carlo analysis based on sensitive parameters identified at 24 h after drug administration was 41 d, which was similar to 43 d calculated using the tolerance limit method. Sensitivity analysis identified two additional sensitive parameters at 6 weeks: intestinal transit rate constant and urinary elimination rate constant. The predicted WT in muscle + skin based on sensitive parameters identified at 6 weeks was 54 d. This model provides a useful tool to estimate tissue residues and withdrawal times for doxycycline in grass carp and also serves a foundation for extrapolation to other fish species and other tetracyclines. Graphical abstract: Image 1 Highlights: Cardiac output and organ weights of grass carp were determined. A PBPK model of doxycycline in grass carp was developed for food safety assessment. The withdrawal times were estimated based on sensitive parameters identified at 24 or 1008 h. The model provides a basis for extrapolation to other fish species and other tetracyclines.