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土霉素在反刍动物中的年龄依赖性药代动力学

Age-dependent pharmacokinetics of oxytetracycline in ruminants.

作者信息

Nouws J F, van Ginneken C A, Ziv G

出版信息

J Vet Pharmacol Ther. 1983 Mar;6(1):59-66. doi: 10.1111/j.1365-2885.1983.tb00455.x.

Abstract

Oxytetracycline (OTC) was administered intravenously (i.v.) to 3- and 12-week-old calves and lactating cows, and both i.v. and intramuscularly (i.m.) to 14-week-old calves and non-lactating cows. Concentrations of OTC were determined in plasma and were analysed kinetically. The pharmacokinetic parameters which were derived using the three-compartment open model were inadequate to describe plasma drug levels in six out of the 23 animals treated i.v., and, therefore, model-independent kinetic parameters were utilized for evaluating age-dependent pharmacokinetics of OTC. In the 3-week-old calves, the total body clearance (ClB) was 0.0022 ml/min/kg, the total distribution volume (Vd area) was 2.48 l/kg, and the distribution volume of the central compartment (V1) was 0.56 l/kg. Mean values for ClB, Vd area, and V1 in 3-week-old calves were two-, three- and four-fold greater, respectively, than the corresponding values in cows. Mean values of ClB and Vd area for the 12- and 14-week-old calves were intermediate between the corresponding values in 3-week-old calves and cows. Dose and state of lactation did not affect the model-independent parameters. The i.v. and i.m. data illustrated that the recommended dose levels of OTC in young calves should be twice those employed in cows for obtaining similar plasma OTC concentration--time profiles.

摘要

将土霉素(OTC)静脉注射给3周龄和12周龄的犊牛以及泌乳奶牛,并将其静脉注射和肌肉注射给14周龄的犊牛和非泌乳奶牛。测定血浆中土霉素的浓度并进行动力学分析。使用三室开放模型得出的药代动力学参数不足以描述23只接受静脉注射治疗的动物中6只的血浆药物水平,因此,使用与模型无关的动力学参数来评估土霉素的年龄依赖性药代动力学。在3周龄的犊牛中,全身清除率(ClB)为0.0022 ml/min/kg,总分布容积(Vd area)为2.48 l/kg,中央室分布容积(V1)为0.56 l/kg。3周龄犊牛的ClB、Vd area和V1的平均值分别比奶牛的相应值大两倍、三倍和四倍。12周龄和14周龄犊牛的ClB和Vd area平均值介于3周龄犊牛和奶牛的相应值之间。剂量和泌乳状态不影响与模型无关的参数。静脉注射和肌肉注射的数据表明,为了获得相似的血浆土霉素浓度-时间曲线,幼龄犊牛中土霉素的推荐剂量水平应是奶牛的两倍。

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