| The experiment was conducted to study the pharmacokinetics and residual elimination of doxycycline (DOTC) in the Channel Catfish (Ictalurus punctatus) in the different temperature (18±1℃and 28±1℃). At pharmacokinetic groups, after a single oral administration at a dose of 20 mg·kg-1 at0.083,0.167,0.25,0.5,1,2,4,8,12,16,24,48,72,96,120,144 h, channel catfish were killed and the plusma, muscle, liver, kindey tissues were collected (five fish was experimented at each time point). At residual groups, after repeated oral administration for 5 consecutive days, channel catfish were killed and the muscle and skin, liver, kindey tissues were collected after 1,3,5,7,9,12,15,24,30,40 d of oral administration (five fish was experimented at each time point). Doxycycline (DOTC) in plasma and tissues were determined by using high-performance liquid chromatography (HPLC) with UV detection.Pharmacokinetic parameters were calculated by using the 3p97 (Practical Pharmacokinetic Program) software (Mathematics Specisl Field Committee Chinese pharmacology institute,china).The results indicated that:1)The concentration-time course of DOTC in plasma and tissues can all be described by a two-compartment open model after a single oral administration at the different temperature. The kinetic equation were Cplasma=1.6928e-0.2018t和Cplasma=1.3929e-0.1707t respectively at 18℃and 28℃. It showed an obvious double-peak phenomenon. The main pharmacokinetic parameters were as follows:At 28℃and 18℃, the Tmax(1) of doxycycline was about 30 min and 1 h in plasma respectly. The Cmax(1)was 0.58±0.094和1.2765±0.59μg/ml inplasma. The Tmax (1) of doxycycline were both about 1 h in liver,30 min and 1 h in kidney,30 min and 1 h in muscle. The Tmax(2) of doxycycline was 12 h and 48 h in liver,8 h and 16 h in kidney, 8 h and 12 h in muscle. The area under concentration-time curve (AUC) was 63.242,1282.076,142.379,62.348μg·ml-1·h in kidney, liver, plasma, muscle respectively at 28℃. At 28℃,the elimination half-life (T1/2b)was 31.091～48.767 h and the absorption half-life (T1/2(ka)) was 0.207～5.34 h. The AUC was 117.084,3678.676,261.643,100.974μg·ml-1·h in kidney, liver, plasma, muscle respectively at 18℃. At 18℃,the T1/2b was 42.184～73.937 h and the T1/2(ka) was 1.193～11.114 h. The results show that the pharmacokinetics and depletion speed of doxycycline in channel catfish closely relates with the water temperature. The depletion of DOTC residue in channel catfish is faster at higher water temperature. The speed from fast to slow is muscle and skin,kidney,liver. To compare with other tissues, the elimination of DOTC residue in muscle and skin was slowest, liver was the main reservoir of DOTC residue in channel catfish. If take liver as target tissue in this experiment. According to the maximum residue limit (MRL) of 300μg/kg in liver, The withdrawl period should not be less than 55 d and 30 d at 18℃and 28℃under this experiment condition. And if take an edible tissue of muscle and skin as target tissue in this experiment. According to the maximum residue limit (MRL)of 300μg·kg-1 in muscle and skin. The withdrawl period should not be less than 22 d和19 d at 18℃and 28℃respectively.The conclusion was that the pharmacokinetics and depletion speed of doxycycline in channel catfish closely relates with the water temperature. The elimination rate was markedly different in different water temperature at the same tissues or different water temperature at the same tissues(P<0.05). At 18℃, the distribution and eliminate of DOTC was slower than at 28℃in plasma and tissues. The concentration of DOTC in tissues at 28℃were all higher than the lower temperature groups. The CmaX(2) was exceeded than the corresponding Cmax(1) The reliable theory basis to make dosage regimen and withdrawl time at different water temperature based on the study.
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