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犬皮下和口服给药后伊维菌素和多拉菌素的血浆处置比较

Comparative plasma dispositions of ivermectin and doramectin following subcutaneous and oral administration in dogs.

作者信息

Gokbulut Cengiz, Karademir Umit, Boyacioglu Murat, McKellar Quintin A

机构信息

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Adnan Menderes, Isikli Koyu, Aydin, Turkey.

出版信息

Vet Parasitol. 2006 Feb 18;135(3-4):347-54. doi: 10.1016/j.vetpar.2005.10.002. Epub 2005 Nov 8.

Abstract

This study evaluates the comparative plasma dispositions of ivermectin (IVM) and doramectin (DRM) following oral and subcutaneous administration (200 microg/kg) over a 40-day period in dogs. Twenty bitches were allocated by weight in to four groups (Groups I-IV) of five animals each. Animals in the first two groups (Groups I and II) received orally the injectable solutions of IVM and DRM, respectively, at the dose of 200 microg/kg bodyweight. The other two groups (Groups III and IV) received subcutaneously injectable solutions at the same dose rate. Blood samples were collected between 1h and 40 days after treatment and the plasma samples were analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The results indicated that IVM produced a significantly higher maximum plasma concentration (C(max): 116.80+/-10.79 ng/ml) with slower absorption (t(max): 0.23+/-0.09 day) and larger area under the concentration versus time curve (AUC: 236.79+/-41.45 ng day/ml) as compared with DRM (C(max): 86.47+/-19.80 ng/ml, t(max): 0.12+/-0.05 day, AUC: 183.48+/-13.17 ng day/ml) following oral administration of both drugs; whereas no significant differences were observed on the pharmacokinetic parameters between IVM and DRM after subcutaneous administrations. In addition, subcutaneously given IVM and DRM presented a significantly lower maximum plasma concentration (C(max): 66.80+/-9.67 ng/ml and 54.78+/-11.99 ng/ml, respectively) with slower absorption (t(max): 1.40+/-1.00 day and 1.70+/-0.76 day, respectively) and larger area under the concentration versus time curve (AUC: 349.18+/-47.79 ng day/ml and 292.10+/-78.76 ng day/ml, respectively) as compared with the oral administration of IVM and DRM, respectively. No difference was observed for the terminal half-lives ((t(1/2lambda(z)) and mean residence times (MRT) of both molecules. Considering the pharmacokinetic parameters, IVM and DRM could be used by the oral or subcutaneous route for the control of parasitic infection in dogs.

摘要

本研究评估了伊维菌素(IVM)和多拉菌素(DRM)在犬类中经口和皮下给药(200微克/千克)后40天内的血浆处置情况比较。将20只母犬按体重分为四组(I-IV组),每组五只动物。前两组(I组和II组)动物分别按200微克/千克体重的剂量经口给予IVM和DRM的注射溶液。另外两组(III组和IV组)以相同剂量皮下注射溶液。在治疗后1小时至40天之间采集血样,并使用荧光检测通过高效液相色谱法(HPLC)分析血浆样品。结果表明,与DRM相比,IVM口服给药后产生的最大血浆浓度(C(max):116.80±10.79纳克/毫升)显著更高,吸收较慢(t(max):0.23±0.09天),浓度-时间曲线下面积更大(AUC:236.79±41.45纳克·天/毫升)(DRM的C(max):86.47±19.80纳克/毫升,t(max):0.12±0.05天,AUC:183.48±13.17纳克·天/毫升);而皮下给药后IVM和DRM的药代动力学参数未观察到显著差异。此外,与IVM和DRM经口给药相比,皮下给予IVM和DRM的最大血浆浓度显著更低(C(max)分别为66.80±9.67纳克/毫升和54.78±11.99纳克/毫升),吸收较慢(t(max)分别为1.40±1.00天和1.70±0.76天),浓度-时间曲线下面积更大(AUC分别为349.18±47.79纳克·天/毫升和292.10±78.76纳克·天/毫升)。两种分子的末端半衰期((t(1/2lambda(z))和平均驻留时间(MRT)未观察到差异。考虑到药代动力学参数,IVM和DRM可通过口服或皮下途径用于控制犬类的寄生虫感染。

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