The Pharmacokinetics of Doxycycline in Channel Catfish (Ictalurus punctatus) Following Intravenous and Oral Administrations

Ning Xu; Yu Fu; Bo Cheng; Yongtao Liu; Qiuhong Yang; Jing Dong; Yibin Yang; Shun Zhou; Yi Song; Xiaohui Ai

doi:10.3389/fvets.2020.577234

The Pharmacokinetics of Doxycycline in Channel Catfish (Ictalurus punctatus) Following Intravenous and Oral Administrations

Front Vet Sci. 2020 Nov 5:7:577234. doi: 10.3389/fvets.2020.577234. eCollection 2020.

Authors

Ning Xu^{1

2

3}, Yu Fu⁴, Bo Cheng^{3

5}, Yongtao Liu^{1

2

3}, Qiuhong Yang^{1

2

3}, Jing Dong^{1

2

3}, Yibin Yang^{1

2

3}, Shun Zhou^{1

2

3}, Yi Song^{3

5}, Xiaohui Ai^{1

2

3}

Affiliations

¹ Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, China.
² Hu Bei Province Engineering and Technology Research Center of Aquatic Product Quality and Safety, Wuhan, China.
³ Key Laboratory of Control of Quality and Safety for Aquatic Products, Ministry of Agriculture and Rural Affairs, Beijing, China.
⁴ Food Engineering College, Hunan University of Arts and Science, Changde, China.
⁵ Aquatic Products Quality and Standards Research Center, Chinese Academy of Fishery Sciences, Beijing, China.

Abstract

The objective of this study was to investigate the bioavailability (BA) and pharmacokinetics (PK) of doxycycline (DC) in channel catfish (Ictalurus punctatus) following a single intravenous injection at 5 mg/kg and a single oral administration at 50 mg/kg at 24°C. The calculation of PK parameters was based on the software 3P97. The plasma samples were determined using ultra-performance liquid chromatography. Following oral administration, the multiple-peak phenomenon presented in concentration vs. time curve of DC at 2 h (107.01 mg/L), 8 h (55.07 mg/L), and 72 h (15.10 mg/L), respectively. The compartmental model cannot simulate the oral concentration vs. time profile beside a non-compartmental model. The calculated parameters of the elimination rate constant (λ_z), the elimination half-life (t_1/2λz ), and the area under the concentration vs. time curve (AUC_0-144) were 0.037 1/h, 18.91 h, and 2255.45 μg.h/mL, respectively. After intravenous administration, the concentration vs. time profile of DC was best described by a two-compartmental open model without absorption. The parameters of the distribution rate constant (α), the distribution half-life (t_1/2α), the elimination rate constant (β), the elimination half-life (t_1/2β), the apparent distribution volume at steady state (V_ss), the total clearance (Cl) and the area under the concentration vs. time curve (AUC_0-∞) were 2.79 1/h, 0.25 h, 0.042 1/h, 16.51 h, 300.00 mL/kg, 14.00 mL/h/kg, and 364.99 μg.h/mL, respectively. For the calculation of BA values at the same condition, the data obtained from intravenous injection were also iterated based on a non-compartmental model, and the corresponding parameters of λ_z, t_1/2λz , V_z, Cl, and AUC_0-144 were 0.019 1/h, 36.26 h, 480.00 mL/kg, 9.10 mL/h/kg, and 514.45 μg.h/mL, respectively. However, there was a considerable difference in the same parameter when calculated by compartmental and non-compartmental approaches. Finally, the medium BA value of DC was evaluated to be 43.84%. This study provides future studies with a framework for determining the BA of DC in the development of a new formulation and provides information on the appropriate use of DC in aquaculture.

Keywords: bioavailability; channel catfish; doxycycline; non-compartmental model; pharmacokinetics.