Womble Ariel Y, Giguère Steeve, Lee Elise A, Vickroy Thomas W
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136, USA.
Am J Vet Res. 2006 Oct;67(10):1681-6. doi: 10.2460/ajvr.67.10.1681.
To determine pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar (BAL) cells of foals.
6 healthy 2-to 3-week-old foals.
In a crossover design, clarithromycin (7.5 mg/kg) was administered to each foal via IV and intragastric (IG) routes. After the initial IG administration, 5 additional doses were administered IG at 12-hour intervals. Concentrations of clarithromycin and its 14-hydroxy metabolite were measured in serum by use of high-performance liquid chromatography. A microbiologic assay was used to measure clarithromycin activity in serum, urine, peritoneal fluid, synovial fluid, CSF, pulmonary epithelial lining fluid (PELF), and BAL cells.
After IV administration, elimination half-life (5.4 hours) and mean +/- SD body clearance (1.27 +/- 0.25 L/h/kg) and apparent volume of distribution at steady state (10.4 +/- 2.1 L/kg) were determined for clarithromycin. The metabolite was detected in all 6 foals by 1 hour after clarithromycin administration. Oral bioavailability of clarithromycin was 57.3 +/- 12.0%. Maximum serum concentration of clarithromycin after multiple IG administrations was 0.88 +/- 0.19 microg/mL. After IG administration of multiple doses, clarithromycin concentrations in peritoneal fluid, CSF, and synovial fluid were similar to or lower than concentrations in serum, whereas concentrations in urine, PELF, and BAL cells were significantly higher than concentrations in serum.
Oral administration of clarithromycin at 7.5 mg/kg every 12 hours maintains concentrations in serum, PELF, and BAL cells that are higher than the minimum inhibitory concentration (0.12 microg/mL) for Rhodococcus equiisolates for the entire 12-hour dosing interval.
测定克拉霉素在幼驹体内的药代动力学以及其在体液和支气管肺泡(BAL)细胞中的浓度。
6匹健康的2至3周龄幼驹。
采用交叉设计,通过静脉注射(IV)和胃内(IG)途径给每匹幼驹给予克拉霉素(7.5mg/kg)。首次胃内给药后,每隔12小时再给予5次胃内给药。采用高效液相色谱法测定血清中克拉霉素及其14 - 羟基代谢物的浓度。采用微生物学测定法测定血清、尿液、腹腔液、滑液、脑脊液、肺上皮衬液(PELF)和BAL细胞中克拉霉素的活性。
静脉注射后,测定了克拉霉素的消除半衰期(5.4小时)、平均±标准差的机体清除率(1.27±0.25L/h/kg)和稳态分布容积(10.4±2.1L/kg)。在克拉霉素给药后1小时,在所有6匹幼驹中均检测到了代谢物。克拉霉素的口服生物利用度为57.3±12.0%。多次胃内给药后克拉霉素的最大血清浓度为0.88±0.19μg/mL。多次胃内给药后,腹腔液、脑脊液和滑液中克拉霉素的浓度与血清中的浓度相似或低于血清浓度,而尿液、PELF和BAL细胞中的浓度显著高于血清浓度。
每12小时口服7.5mg/kg克拉霉素可使血清、PELF和BAL细胞中的浓度在整个12小时给药间隔内高于马红球菌分离株的最低抑菌浓度(0.12μg/mL)。