Study On The Pharmacokinetics And Residues Elimination Of Diclofenac Sodium Injection In Pigs

Diclofenac sodium (DS) is the third generation non-steroidal anti-inflammatory drugs with properties of analgesic, anti-inflammatory and antipyretic. DS is widely used in the pharmaceutical industry due to its characteristics of taking action faster, long-lasting potency, better efficacy, little side effects and no accumulation. The mechanism of DS was to block arachidonic acid conversion to prostaglandins by inhibition of cyclooxygenase activity. The synthesis of leukotriene was inhibited by DS through promoting arachidonic acid binding triglyceride. The pharmacokinetics characteristics and residue elimination of DS injection in pigs were studied in this paper, in order to provide experimental evidence for the rational use of drugs and withdrawal time to ensure animal food safety and consumer health.1 Pharmacokinetic characteristics of DS injection in pigsEight piglets(4+4) were randomly divided into two groups. The pharmacokinetics of 5% DS injection were studied with cross-over study design. The weaned piglets were intravenously and intramuscularly administrated at the dose of 2.5 mg/kg body weight. The blood samples were collected at predetermined time, and then extracted with ether.1.5% acetic acid and methanol were used as the mobilephase for high performance liquid chromatography (HPLC). Pharmacokinetic parameters were obtained by DAS2.1.1 pharmacokinetic analysis software.After single intravenous administration of 5%DS injection, the main pharmacokinetic parameters of DS were as follow:T1/2β was 1.32 h, the Tmax and Cmax were 0.10 h and 37.69 μg/mL, MRT was 1.60 h, the AUC was 55.50 hr·μg/mL, Vd was 0.50 L/kg, and CLB was about 0.26 L/h/Kg. After a single dose of intramuscular injection of 5% DS injection, T1/2β was 1.87 h, the Tmax and Cmax were 1.19 h and 11.61 μg/mL, MRT was about 2.86 h, AUC was about 43.17 hr·μg/mL, and the absolute bioavailability was 78.50%, The results indicated that diclofenac was eliminated quickly and the distribution was poor in vivo. After intramuscular administration, the drug was absorbed rapidly and well.2 The residues elimination of DS injection in pigs by intramuscular administrationDiclofenac in edible tissues of pigs were extracted with ethyl acetate and determined by a validated high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method. Acetonitrile and 0.2 mM ammonium acetate solution (70:30, V/V/V) were used as the mobile phase.Mean recoveries of Diclofenac in porcine tissues(muscle, liver, kidney and serum) fortified at 0.5、5 and 50μg/kg were 70% to 120%, with in-day and between-day coefficients of varination less than 10%. The concentration of diclofenac within the range of 0.5-100 ng/mL in tissues showed a good liner relation with the linear correlation coefficients more than 0.99.The limits of detection(LOD) andThe limit of quantification(LOQ) in edible tissues of pigs were 0.1 μg/kg and 0.5μg/kg respectively. The method complied with the requirement for diclofenac residue analysis.25 health York white pigs with mean body weight of 50 kg received 3 consecutive intramuscular injection of 2.5 mg/kg b.w. diclofenac in the neck once a day. The pigs were sacrificed at 12 h、3d、5d、7d and 12 d following the administration of the last administration. The result showed that except for the injection site, the residual of diclofenac in liver was highest and lowest in kidney after 12 h. After 5 d withdrawal period, the residues of diclofenac in five porcine muscle were all below the LOQ. The residues of diclofenac in four porcine sebum were all below the LOQ after 7d, but all above the LOQ in all five porcine liver and kidney. The result showed that the liver was the target organ and diclofenac residue concentrations in muscle and sebum were decreased quickly, however, in liver and kidney were decreased slowly. The data were analysed with WT1.4 program. The withdrawal period was 9.892 d in liver、5.116d in kidney、14.205 d in sebum、5.444 d in muscle tissue and 8.818 d in injection site muscle. According to the double-sided 95% confidence interval, the withdrawal period of DS injection in the pig was 15 days.