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皮下注射头孢噻呋钠后,犬体内头孢噻呋及其代谢物的血浆和尿液处置及剂量比例关系

Plasma and urine disposition and dose proportionality of ceftiofur and metabolites in dogs after subcutaneous administration of ceftiofur sodium.

作者信息

Brown S A, Arnold T S, Hamlow P J, Speedy A K, Deleeuw N L, Hubbard V L, Callahan J K, Folz S D, Janose R L, Flook T F

机构信息

Animal Health Drug Metabolism, Upjohn Company, Kalamazoo, MI 49001, USA.

出版信息

J Vet Pharmacol Ther. 1995 Oct;18(5):363-9. doi: 10.1111/j.1365-2885.1995.tb00605.x.

Abstract

Nine male dogs (10.3-13.5 kg body weight) were randomly assigned to three groups of three dogs each and administered ceftiofur sodium subcutaneously as a single dose of 0.22, 2.2, or 4.4 mg ceftiofur free acid equivalents/kg body weight. Plasma and urine samples were collected serially for 72 h and assayed for ceftiofur and metabolites (derivatized to desfuroylceftiofur acetamide) using high-performance liquid chromatography. Urine concentrations remained above the MIC90 for Escherichia coli (4.0 micrograms/mL) and Proteus mirabilis (1.0 micrograms/mL) for over 24 h after doses of 2.2 mg/kg (8.1 micrograms/mL) and 4.4 mg/kg (29.6 micrograms/mL), the interval between treatments for ceftiofur sodium in dogs, whereas urine concentrations 24 h after dosing at 0.22 mg/kg (0.1 mg/Ib) were below the MIC90 for E. coli and P. mirabilis (0.6 microgram/mL). Plasma concentrations were dose-proportional, with peak concentrations of 1.66 +/- 0.0990 micrograms/mL, 8.91 +/- 6.42 micrograms/mL, and 26.7 +/- 1.07 micrograms/mL after doses of 0.22, 2.2, and 4.4 mg/kg, respectively. The area under the plasma concentration versus time curve, when normalized to dose, was similar across all dosage groups.

摘要

九只雄性犬(体重10.3 - 13.5千克)被随机分为三组,每组三只,分别皮下注射头孢噻呋钠,剂量为每千克体重0.22、2.2或4.4毫克头孢噻呋游离酸当量。连续72小时采集血浆和尿液样本,使用高效液相色谱法测定头孢噻呋及其代谢物(衍生化为去呋喃甲酰头孢噻呋乙酰胺)。剂量为2.2毫克/千克(8.1微克/毫升)和4.4毫克/千克(29.6微克/毫升)后,尿液浓度在超过24小时内保持高于大肠杆菌(4.0微克/毫升)和奇异变形杆菌(1.0微克/毫升)的MIC90,这是犬用头孢噻呋钠治疗间隔时间;而剂量为0.22毫克/千克(0.1毫克/磅)给药24小时后的尿液浓度低于大肠杆菌和奇异变形杆菌的MIC90(0.6微克/毫升)。血浆浓度与剂量成比例,剂量分别为0.22、2.2和4.4毫克/千克时,峰值浓度分别为1.66±0.0990微克/毫升、8.91±6.42微克/毫升和26.7±1.07微克/毫升。将血浆浓度-时间曲线下面积按剂量归一化后,所有剂量组相似。

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