Prado Maria E, Ryman Josiah T, Boileau Melanie J, Martin-Jimenez Tomas, Meibohm Bernd
Department of Animal Science, Institute of Agriculture, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Am J Vet Res. 2011 Oct;72(10):1386-9. doi: 10.2460/ajvr.72.10.1386.
To determine the pharmacokinetics after oral administration of a single dose of ponazuril to healthy llamas.
6 healthy adult llamas.
Ponazuril (20 mg/kg) was administered once orally to 6 llamas (day 0). Blood samples were obtained on days 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 14, 21, 28, 35, 42, and 49. Serum ponazuril concentrations were determined by use of a validated reverse-phase high-performance liquid chromatography assay with UV absorbance detection. Pharmacokinetic parameters were derived by use of a standard noncompartmental pharmacokinetic analysis.
Mean ± SD area under the serum concentration-time curve was 7,516 ± 2,750 h•mg/L, maximum serum ponazuril concentration was 23.6 ± 6.0 mg/L, and the elimination half-life was 135.5 ± 16.7 hours. Serum concentration of ponazuril peaked at 84 hours (range, 48 to 120 hours) after administration and gradually decreased but remained detectable for up to 35 days after administration. No adverse effects were observed during the study period.
The rate and extent of absorption following oral administration of a single dose of ponazuril were sufficient to result in potentially effective concentrations, and the drug was tolerated well by llamas. At this dose, ponazuril resulted in serum concentrations that were high enough to be effective against various Apicomplexans on the basis of data for other species. The effective ponazuril concentration that will induce 50% inhibition of parasite growth for Eimeria macusaniensis in camelids is currently unknown.
确定健康美洲驼单次口服泊那唑后的药代动力学。
6只健康成年美洲驼。
对6只美洲驼(第0天)口服一次泊那唑(20mg/kg)。在第0、0.5、1、2、3、4、5、6、7、9、11、14、21、28、35、42和49天采集血样。采用经过验证的反相高效液相色谱法并结合紫外吸光度检测来测定血清泊那唑浓度。通过标准的非房室药代动力学分析得出药代动力学参数。
血清浓度 - 时间曲线下面积的平均值±标准差为7516±2750h•mg/L,血清泊那唑最大浓度为23.6±6.0mg/L,消除半衰期为135.5±16.7小时。给药后84小时(范围为48至120小时)血清泊那唑浓度达到峰值,随后逐渐下降,但在给药后长达35天仍可检测到。研究期间未观察到不良反应。
单次口服泊那唑后的吸收速率和程度足以产生潜在的有效浓度,且美洲驼对该药物耐受性良好。基于其他物种的数据,在此剂量下,泊那唑产生的血清浓度足以有效对抗各种顶复门原虫。目前尚不清楚对骆驼科动物的马库萨尼艾美耳球虫产生50%寄生虫生长抑制作用的泊那唑有效浓度。