Pharmacokinetic Profile and Muscle Residue Elimination of Tilmicosin after Oral Administration in Crucian Carp (Carassius auratus)

Abstract

The aim of this study was to investigate the pharmacokinetics and muscle tissue residue elimination of tilmicosin (TLM) in crucian carp (Carassius auratus) at water temperature of 26±1°C after administration of TLM at three different doses. The crucian carp were randomly divided into two treatment groups and a control group. TLM was administered at two different doses to the treatment groups. Group 1 received a single orally administered dose of TLM at the rate of 50mg/kg body weight, group 2 received three orally administered doses of TLM at the rate of 50 mg/kg body wt. on three consecutive days and Group 3 (the control group) received a normal, drug free diet (0 TLM). TLM concentrations in plasma and muscle tissue were analyzed with ultra highperformance liquid chromatography (UPLC, Waters, USA). Using the 3p97 software, the data of pharmacokinetics was conformed to a two-compartment model. The absorption rate constant (Ka) and absorption half-life (t1/2 kα) of TLM were 1.99 h and 0.349 h, respectively. The distribution half-life (t1/2α) and elimination half-life (t1/2β) of TLM were 2.87 h and 39.89 h, respectively. The maximum concentration (Cmax) of TLM in plasma was 19.36 μg/ml and the time to peak concentration (Tp) was 1.27 h. The area under the plasma concentration-time curve (AUC) was 240.326 µg·h/ml. The distribution volume (Vd/F) of TLM was calculated as 1.968 l/kg. for determination of the muscle residue elimination of TLM used by oral administration at a dosage of 50 mg/kg body weight per day for 3 days of TLM. The results revealed that the elimination of TLM in the crucian carp muscle tissue has a long half-life time of 3.12 d. Based on the above residues, we suggest the withdrawal time should be at least 33 days, calculated by the equation MRL=C0 ek(WDT).