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In this study, the plasma pharmacokinetics and tissue disposition of sulfadiazine (SDZ) and its main metabolite, N₄-acetyl sulfadiazine (ACT-SDZ), were compared between 18 and 24 °C following a single oral administration of SDZ at 50 mg/kg in grass carp (<i>Ctenopharyngodon idella</i>). The plasma and tissues were sampled from 0.167 h up to 96 h and analyzed by ultra-performance liquid chromatography with an ultraviolet detector. The pharmacokinetic parameters were estimated using a one-compartmental approach. Results showed that pharmacokinetics of SDZ and ACT-SDZ in plasma and tissues were notably influenced by the increase of temperature. The increased temperature shortened the absorption half-life (K01_HL) of SDZ and ACT-SDZ in gill, kidney, and plasma, but increased in liver and muscle + skin. The elimination half-life (K10_HF) and the area under concentration-time curve (AUC_0–∞) of SDZ and ACT-SDZ all presented a declined trend. The apparent volume of distribution (V_F) of SDZ in plasma was increased from 0.93 to 1.64 L/kg, and the apparent systemic total body clearance (Cl_F) was also increased from 0.01 to 0.05 L/h/kg. Overall, the rise of temperature decreased K10_HF, AUC_0–∞ of SDZ, and ACT-SDZ in plasma and tissues, but increased V_F and Cl_F in the plasma for SDZ.