Title: Effect of temperature on plasma and tissue kinetics of doxycycline in grass carp (Ctenopharyngodon idella) after oral administration
Abstract: The objective of this study was to evaluate the effect of temperature (18 versus 24 °C) on doxycycline (DC) plasma pharmacokinetics and tissue disposition in grass carp (Ctenopharyngodon idella) after single oral administration at 20 mg/kg. The concentrations of DC in the plasma and tissues (gill, liver, kidney, and muscle+skin) at a series of pre-determined time points up to 168 h after dosing were measured. The pharmacokinetic parameters were calculated using a non-compartmental approach. The results showed that the temperature prominently affected DC's plasma pharmacokinetics and tissue disposition kinetics in grass carp. Comparing 18 °C and 24 °C, the terminal half–life (T1/2λz) was almost the same in the plasma (21.70 vs. 20.10 h), but was decreased from 27.80 to 17.93, from 51.58 to 37.56, from 66.17 to 23.68, and from 30.08 to 24.22 h for liver, kidney, gill, and muscle+skin, respectively. The time to peak concentration (Tmax) in the gill, kidney and muscle+skin was shortened, but it was not changed in plasma or liver. The peak concentrations (Cmax) in tissues were decreased (e.g., from 119.28 to 49.22 mg/L in liver), but was increased from 17.01 to 89.68 mg/L in plasma. A similar decreasing trend was observed in the area under the concentration curve (AUClast) of gill, kidney, liver and muscle+skin, while the AUClast of plasma was increased. Overall, the increase of temperature decreased the tissue T1/2λz, Cmax, and AUClast, while in the plasma it increased Cmax, AUClast, and decreased plasma clearance. The present study provides insight into the design of therapeutic regimens of DC in grass carp at two different temperatures to avoid treatment failure and risk of drug resistance. The results can also be used to develop physiologically based pharmacokinetic models to predict tissue residues and withdrawal intervals.
Publication Year: 2019
Publication Date: 2019-09-01
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 30
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