Pharmacokinetics And Residues Of Hydrochloric Valnemulin Following Oral Administration In Swine

Pharmacokinetics and residue of hydrochloric valnemulin (VLM) were studied in pigs following oral administration. VLM concentrations in plasma and tissues were analyzed after liquid-liquid extraction sample pretreatment steps using reversed-phase high-performance liquid chromatography (RP-HPLC). The correlation of calibration curves were all good, which correlation coeffcients (r) were above 0.9969. The average extraction recoveries were more than 85% from plasma, more than 75% from muscle, fat, liver and kidney. The intra-day and inter-day coefficients of variation were less than 7% and 10%, respectively. The limits of detection (LOD) were 0.025μg/mL,0.025μg/g, 0.025μg/g,0.0625μg/g and 0.0625μg/g in plasma, muscle, fat, liver and kidney, respectively. The limits of quantitation (LOQ) were 0.05μg/mL,0.05μg/g,0.05μg/g, 0.1μg/g and 0.1μg/g in the corresponding tissues, respectively.Pigs were administered orally with a single dosage of 12mg/kg body weight in the pharmacokinetics group. The results revealed that the pharmacokinetic characteristics of VLM in pigs manifested rapid absorption, wide distribution and short elimination half-lives. The plasma concentration-time data conformed to one-compartment open models. Pharmacokinetic equations was C=5.66(e"032t-e-0.52t). The distribution half-lives of VLM (t1/2a) was 1.32h. The elimination half-lives (t1/2β) was 2.10h. The absorption rate constant (Ka) was 0.52b-1; The elimination rate constan (Ke) was 0.32h-1; The maximum plasma concentration (Cmax) and the time of maximum plasma concentration (Tmax) were detected to be 1.78μg/mL and 2.38h. The bioavailability (F) was 83%; The areas under the concentration-time curve (AUC) was 6.81μg·h/mL.Twenty-four healthy pigs were administered valnemulin hydrochloric at a dosage of 200 mg/kg for 21 days. Four pigs were slaughtered at 0,6,12,18,24,36 hours after the last feeding. Tissues including kidney, liver, muscle and fat of each pig were collected to determine VLM concentrations. The results showed that the residue of valnemulin hydrochloric in liver was the highest, and lower in kidney. The residues of valnemulin hydrochloric in muscle and fat were much lower than that in liver and kidney, residues were declined below the LOQ at 24h, and dropped to LOD at 36h of withdrawal period. Comparing with the other tissues, the elimination of VLM in kidney was slowest, which behaved as a reservoir in pigs.The pharmacokinetics study showed that after a single oral dosage of 12mg/kg body weight in pigs, the pharmacokinetic characteristics of VLM showed rapid absorption, wide distribution and short elimination half-lives. Based on the results of the residue study, the depletion of VLM in porcine tissues was fast and the withdrawal periods for all porcine tissues were two days in order to make the tissues safe for consumption.