| Bioequivalence is in order to verify that the drugs produced by two different pharmaceutical companies, which contain the same active ingredient, or are the same product in two different formulation, while in clinical use, they are absorbed into the animals at the same rate and degree, show similar bioavailability and the same efficacy, if they can be used interchangeably in clinical alternative. The oxytetracycline is a natural tetracycline antibiotics, with good pharmacokinetic characteristic, low residues in body and less side effects. It’s a good broad-spectrum antibiotics. The aim of this experiment is to study the bioequivalence of the two kinds of20%of long-acting oxytetracycline injection in pigs.AIM:To establish the method of detection Oxytetracycline after extraction from the plasma of pigs, using HPLC. And to study the absorption, distribution, pharmacokinetics and bioequivalence of the drugs in the plasma of pigs. In order to provide evidence for clinical veterinary safety of medication.METHODS:This research has been carried out by using a two-period cross-over method. The24test animals (30±5)kg were randomly divided into two groups, testing group and reference group. The testing group was administered via intramuscular injection of20%Oxytetracyline Injection made by Intervet Company in the first period, and followed by injection made by Pfizer Company in the second period; the referencing group, on the contrary, was first administered by Pfizer Company, and followed by Intervet Company. The dose was20mg/kg body weight, then plasma samples were collected in different intervals. There was a washout time of14d between the two periods. The samples were determined by using HPLC after liquid-Phase extraction. The concentration-time data of drugs in Plasma were analyzed with3P97Pharmacokinetics Program, and ANOVA was used for statistical analysis. Two-one sided t-tests and90%of confidence interval of AUC0-144、AUC0-∞and Cmax. Bioequivalence evaluation of Tmax is statistically analyzed with nonparametric test. RESULTS:This research has established the method of detection Oxytetracycline after extraction from the Plasma of pigs, using HPLC. The correlations of calibration curve were all good, while correlations of coefficient were0.9999. Oxytetracycline the limit of detection (LOD) and quantification (LOQ) were0.025μg/mL and0.05μg/mL in plasma respectively. The average extraction recovery was more than85%from the Plasma. The inter-day coefficient of variations and inter-day coefficient of Variations were less than5%and10%, respectively. The pigs received intramuscular injection of20%Oxytetracyline Injection (20mg/kg). The results indicated the Plasma drug concentration-time data was fitted two-compartment open models. The parameters, for testing and referencing, respectively, were as followings:AUC0-144(118.926±3.259)μg-h/mL and (126.179±17.390)μg-h/mL; AUC0-∞(123.087±13.906)μg-h/mL and (130.732±18.562)μg-h/mL; Cmax(5.066±0.486)μg/mL and (5.071±0.877)μg/mL; Tmax(0.740±0.278)h and (0.650±0.258)h, F (94.291±15.287)%.There was no significant difference between formation, between period and between individual after ANOVA of AUC0-144、AUC0-∞and Cmax(P>0.05). There was significant difference between t1and t2after two-one sided t-tests of AUCo-144、AUC0-∞and Cmax(P<0.05). The90%of confidence interval of AUC0-144was99.6%-100.7%fell within the reference range of80%-125%. The90%of confidence interval of AUC0-∞was92.0%～102.1%fell within the reference range of80%-125%. The90%of confidence interval of Cmax was91.9%～107.2%fell within the reference range of70%-143%. Bioequivalence evaluation of Tmax is statistically analyzed with nonparametric test, there was no statistical difference between the two groups (P>0.05).In conclusion, this research has established the HPLC detection method of Oxytetracycline after extraction from the Plasma of pigs. And clarified two kinds of products was in similar pharmacokinetics of pigs. The statistics showed that two products were pharmacokinetic bioequivalence in pigs. |
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