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阿奇霉素在球蟒(皇蟒)体内的药代动力学及组织浓度

Pharmacokinetics and tissue concentrations of azithromycin in ball pythons (Python regius).

作者信息

Coke Rob L, Hunter Robert P, Isaza Ramiro, Koch David E, Goatley Marie A, Carpenter James W

机构信息

Zoological Pharmacology Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.

出版信息

Am J Vet Res. 2003 Feb;64(2):225-8. doi: 10.2460/ajvr.2003.64.225.

Abstract

OBJECTIVE

To determine pharmacokinetics and tissue concentrations of azithromycin in ball pythons (Python regius) after IV or oral administration of a single dose.

ANIMALS

2 male and 5 female ball pythons.

PROCEDURES

Using a crossover design, each snake was given a single dose of azithromycin (10 mg/kg) IV. After a 4-week washout period, each snake was given a single dose of azithromycin (10 mg/kg) orally. Blood samples were collected prior to dose administration and 1, 3, 6, 12, 24, 48, 72, and 96 hours after azithromycin administration. Azithromycin was quantitated by use of liquid chromatography-mass spectrometry.

RESULTS

After IV administration, azithromycin had an apparent volume of distribution of 5.69 L/kg and a plasma clearance of 0.19 L/h/kg. Harmonic means for the terminal half-life were 17 hours following IV administration and 51 hours following oral administration. Mean residence times were 37 and 94 hours following IV and oral administration, respectively. Following oral administration, azithromycin had a peak plasma concentration (Cmax) of 1.04 microg/mL, a time to Cmax of 8.4 hours, and a prolonged mean absorption time of 57 hours. Mean oral bioavailability was 77%. Tissue concentrations ranged from 4 to 140 times the corresponding plasma concentration at 24 and 72 hours after azithromycin administration.

CONCLUSIONS AND CLINICAL RELEVANCE

Azithromycin is well absorbed and tolerated by ball pythons. On the basis of plasma pharmacokinetics and tissue concentration data, we suggest an azithromycin dosage in ball pythons of 10 mg/kg, orally, every 2 to 7 days, depending upon the site of infection and susceptibil ity of the infective organism.

摘要

目的

确定单剂量静脉注射或口服阿奇霉素后球蟒(球蟒属)体内的药代动力学及组织浓度。

动物

2只雄性和5只雌性球蟒。

方法

采用交叉设计,每只蛇静脉注射单剂量阿奇霉素(10毫克/千克)。在4周的洗脱期后,每只蛇口服单剂量阿奇霉素(10毫克/千克)。在给药前以及阿奇霉素给药后1、3、6、12、24、48、72和96小时采集血样。使用液相色谱 - 质谱法对阿奇霉素进行定量。

结果

静脉注射后,阿奇霉素的表观分布容积为5.69升/千克,血浆清除率为0.19升/小时/千克。静脉注射后终末半衰期的调和均值为17小时,口服后为51小时。静脉注射和口服后的平均驻留时间分别为37小时和94小时。口服后,阿奇霉素的血浆峰浓度(Cmax)为1.04微克/毫升,达峰时间为8.4小时,平均吸收时间延长至57小时。平均口服生物利用度为77%。在阿奇霉素给药后24小时和72小时,组织浓度为相应血浆浓度的4至140倍。

结论及临床意义

阿奇霉素在球蟒体内吸收良好且耐受性良好。根据血浆药代动力学和组织浓度数据,我们建议球蟒阿奇霉素的给药剂量为10毫克/千克,口服,每2至7天一次,具体取决于感染部位和感染病原体的易感性。

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