Banting A L, Baggot J D
CEBIPHAR, Fondettes, France.
J Vet Pharmacol Ther. 1996 Feb;19(1):50-5. doi: 10.1111/j.1365-2885.1996.tb00008.x.
The pharmacokinetic properties and local tolerance of three oxytetracycline formulations, one conventional (Engemycine, 10%) and two long-acting (Oxyter LA, 20% and Terramycin LA, 20%) were compared in clinically healthy cross-bred pigs following intramuscular injection of single doses (20 mg/kg body weight) in the neck region. Non-compartmental methods were used to calculate the pharmacokinetic parameters. Assessment of local tolerance was based on serum creatine phosphokinase (CPK) concentration and a combination of echographical, macroscopic and histological examinations of the intramuscular injection site. Statistically significant differences (one-way analysis of variance, F-test) were obtained between the three formulations in peak plasma concentration, peak time and mean residence time. Area under the curve did not differ significantly between the formulations. Using the Students t-test for paired data, the two long-acting formulations differed significantly in peak plasma concentration and peak time. Both of the long-acting formulations differed significantly from the conventional formulation in the peak time and mean residence time. All three formulations produced an increase in serum CPK concentrations. The increase in CPK concentration was present from 6 to 24 h post treatment for Terramycin LA, from 6 to 72 h for Oxyter LA and from 6 to 96 h for Engemycine (the conventional formulation). Echographical examination of the injection site showed lesions of an inflammatory type up to 96 h after IM injection of the drug products, whereas from 7 days the lesions represented primarily scar formation. Histological examination of tissue from the injection site did not correlate with echographical scores. The results obtained in this study show that the long-acting formulations provide significantly longer mean residence times of oxytetracycline than the conventional formulation, and that local tolerance at the IM injection site was similar for all three formulations under the experimental conditions used in this study. It can be concluded that the long-acting formulations provide the advantage of a longer dosage interval when administered to pigs by intramuscular injection in the neck region at a dose of 20 mg/kg body weight.
在临床健康的杂交猪颈部肌肉注射单剂量(20毫克/千克体重)后,比较了三种土霉素制剂的药代动力学特性和局部耐受性,其中一种是常规制剂(恩诺霉素,10%),两种是长效制剂(长效土霉素,20%和土霉素长效剂,20%)。采用非房室方法计算药代动力学参数。局部耐受性评估基于血清肌酸磷酸激酶(CPK)浓度以及对肌肉注射部位的超声、大体和组织学检查结果。三种制剂在血浆峰浓度、达峰时间和平均驻留时间方面存在统计学显著差异(单因素方差分析,F检验)。各制剂之间的曲线下面积无显著差异。使用配对数据的学生t检验,两种长效制剂在血浆峰浓度和达峰时间上存在显著差异。两种长效制剂在达峰时间和平均驻留时间上与常规制剂均存在显著差异。所有三种制剂均导致血清CPK浓度升高。土霉素长效剂治疗后CPK浓度在6至24小时升高,长效土霉素在6至72小时升高,恩诺霉素(常规制剂)在6至96小时升高。注射部位的超声检查显示,注射药物产品后96小时内存在炎症性病变,而7天后病变主要表现为瘢痕形成。注射部位组织的组织学检查结果与超声评分不相关。本研究结果表明,长效制剂中土霉素的平均驻留时间比常规制剂显著更长,并且在本研究使用的实验条件下,三种制剂在肌肉注射部位的局部耐受性相似可以得出结论,当以20毫克/千克体重的剂量在颈部区域对猪进行肌肉注射时,长效制剂具有给药间隔更长的优势。