| Objective:Many pharmacodynamics and pharmacokinetics studies of ceftiofur in animals have been abroad reported, but comparison of pharmacokinetics in different age animal have been seldom reported.This paper studied on the pharmacokinetics of ceftiofur sodium in healthy animals of different age which richen pharmacokinetic data of ceftiofur and provided a theoretical basis for clinical rational drug use.Methods: Ceftiofur is quickly metabolized to desfuroylceftiofur, and metabolism in plasma, urine and tissues is further metabolized to disulfides, such as desfuroylceftiofur-glutathione-disulfide,desfuroylceftiofur-cysteine-disulfide,3,3-desfuroylceftiofur-disulfide and desfuroylceftiofur-protein, instead of free status and prototype drug. This study established HPLC-DAD method for determination of desfuroylceftiofur in plasma. Plasma sample was extracted using dithioerythritol-phosphate buffer,and then concentrated and purified by SPE course and eluted with methanol. Chromatographic separation was carried out on a XDB-C18 chromatographic column. The mobile phase A consisted of acetonitrile, while the mobile phase B consisted 0.1% trifluoroacetic acid solution.A gradient elution was performed:0min:12%A,88%B;15min:18%A and 82%B;18min: 12%A,88%B;and then balanced to 20min. The flow rate was 0.8mL·min-1, followed by deter mination of the residue by DAD detector at 266nm. The determination was quantitated according to peak area of desfuroylceftiofur. The limit of detection for desfuroylceftiofur was 0.025μg·mL-1,while the limits of quantification was 0.05μg·mL-1.Result: This paper studied pharmacokinetics characteristics of ceftiofur sodium in sucking piglets, care pigs and pregnant sows, and the data were analyzed using PKS pharmacokinetics statistical software, The results showed that the pharmacokinetics of sucking piglets, weaned pigs and pregnant sows all fitted a two-compartment open model with first-order absorption after single intramuscular administration of ceftiofur sodium at a dose of 10mg·Kg-1. The main pharmacokinetic parameters respectively were as follows: Absorption half-life were 0.31±0.22h, 1.3±0.33h and 0.71±0.30h. Distribution half-life were 0.98±0.74h, 2.04±0.47h and 3.89±3.39h. Time to peak concentration were 0.78±0.37h, 2.51±0.52h and 2.08±0.64h.Peak concentration were 18.51±4.65μg·mL-1, 27.57±3.50μg·mL-1 and 41.52±6.90μg·mL-1. The area under the concentration were 261.28±94.22μg·mL-1·h, 363.01±78.53μg·mL-1·h and 750.1±218.1μg·mL-1·h. Apparent volume of distribution were 1.214±0.456L·kg-1, 0.501±0.194L·kg-1 and 0.376±0.163L·kg-1.Clearance rate were 0.053±0.025L·h-1, 0.029±0.006L·h-1 and 0.016±0.004L·h-1.Single-factor analysis of variance showed sucking piglets have shorter absorption half-life and faster peak time than weaned pigs and pregnant sows,and which showed significant differences(P<0.05).Significant difference in the area under the concentration was noted between pregnant sows and other two groups(P<0.01).Howere,there were large difference in peak concentration among sucking piglets, weaned pigs and pregnant sows after single administration of the same dose of ceftiofur sodium(P<0.01).No significant difference in apparent volume of distribution and clearance rate were showed between weaned pigs and pregnant sows(P>0.05), but significant differences were noted when compared with sucking piglets(P<0.05).Conclusion: Results indicated that there were no difference in the best pharmacokinetic model among sucking piglets, weaned pigs and pregnant sows after single administration of ceftiofur sodium,but the main pharmacokinetic parameters were significant differences.Sucking piglets have short absorption half-life, short peak time and faster drug-effect, and then no significant difference in peak time between weaned pigs and pregnant sows exists (P> 0.05). Peak concentration of pregnant sows was obviously higher than sucking piglets and weaned pigs(P<0.01).Apparent volume of distribution in sucking piglets was larger than weaned pigs and pregnant sows, indicating that ceftiofur sodium has strong organization penetration,and widely distributed in sucking piglets.Certain differences in clearance rate of the three groups were noted.Sucking piglets had high clearance rate,performed faster drug clearance,shorter maintaining concentration,lower plasma concentration,which prompted dosage regimen should be appropriate adjusted according to animals of the different ages. The results of this study would be very useful for worked out dosage regimen in different age animals.
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