Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, The Ohio State University, Columbus, Ohio, USA.
J Vet Pharmacol Ther. 2022 Nov;45(6):508-515. doi: 10.1111/jvp.13087. Epub 2022 Jul 28.
The purpose of this study was to evaluate the pharmacokinetics of intravenous (IV) ondansetron in a population of hospitalized dogs exhibiting clinical signs of nausea. The causes of nausea included pancreatitis, gastroenteritis, endocarditis, chemotherapy-induced nausea, diabetes mellitus and ketoacidosis, acute kidney injury with aspiration pneumonia, pyometra, uroabdomen, neoplasia, and hepatopathy. Twenty-four dogs were randomly assigned to one of the following IV ondansetron protocols: 1 mg/kg q12h, 0.5 mg/kg q12h, 1 mg/kg q8h, 0.5 mg/kg q8h. Serum was collected at 0, 0.25, 0.5, 1, 2, 4, 8, 16, and 24 h after the first dose, and nausea scores were recorded at multiple time points. Ondansetron and arginine vasopressin (AVP) concentrations were measured via high-performance liquid chromatography coupled to tandem mass spectrometry and ELISA, respectively. Noncompartmental pharmacokinetic modeling and dose interval modeling were performed. Ondansetron displayed linear pharmacokinetics. In the 0.5 mg/kg group, mean C = 214 ng/ml, AUC = 463 ng/mlh, and calculated half-life was 1.9 h. In the 1 mg/kg group, mean C = 541 ng/ml, AUC = 1057 ng/mlh and calculated half-life was 1.6 h. Serum ondansetron concentrations were not significantly different between dogs that required rescue anti-nausea medication (non-responders) and dogs that did not require rescue therapy (responders). In total, 83.3% of patients in the 0.5 mg/kg q8h, 0.5 mg/kg q12h, and 1 mg/kg q8h groups had improvement in nausea scores. In total, 66.7% of patients in the 1 mg/kg q12h group had improvement in nausea scores. In total, 33% of patients had resolution of nausea in the 0.5 mg/kg q8h, 1 mg/kg q8h, and 1 mg/kg q12h groups, and 16% of patients had resolution of nausea in the 0.5 mg/kg q12h group. AVP concentrations were highly variable and did not correlate with nausea scores. Nausea scores significantly decreased regardless of dosage protocol. AVP was not a reliable biomarker of nausea in this group of dogs.
本研究旨在评估静脉注射（IV）昂丹司琼在出现恶心临床症状的住院犬中的药代动力学。恶心的原因包括胰腺炎、胃肠炎、心内膜炎、化疗引起的恶心、糖尿病酮症酸中毒、伴有吸入性肺炎的急性肾损伤、子宫积脓、尿腹、肿瘤和肝病。24 只狗被随机分配到以下 IV 昂丹司琼方案之一：1mg/kg q12h、0.5mg/kg q12h、1mg/kg q8h、0.5mg/kg q8h。在第一次给药后 0、0.25、0.5、1、2、4、8、16 和 24 小时采集血清，并在多个时间点记录恶心评分。通过高效液相色谱-串联质谱法和酶联免疫吸附法分别测定昂丹司琼和精氨酸加压素（AVP）浓度。进行非房室药代动力学模型和剂量间隔模型分析。昂丹司琼显示线性药代动力学。在 0.5mg/kg 组中，平均 C 为 214ng/ml，AUC 为 463ng/mlh，计算半衰期为 1.9h。在 1mg/kg 组中，平均 C 为 541ng/ml，AUC 为 1057ng/mlh，计算半衰期为 1.6h。需要解救止吐治疗（无反应者）和不需要解救治疗（有反应者）的狗之间，血清昂丹司琼浓度无显著差异。在 0.5mg/kg q8h、0.5mg/kg q12h 和 1mg/kg q8h 组中，83.3%的患者恶心评分得到改善。在 1mg/kg q12h 组中，66.7%的患者恶心评分得到改善。在 0.5mg/kg q8h、1mg/kg q8h 和 1mg/kg q12h 组中，33%的患者恶心缓解，0.5mg/kg q12h 组中 16%的患者恶心缓解。AVP 浓度变化较大，与恶心评分无相关性。无论剂量方案如何，恶心评分均显著降低。AVP 不是该组犬恶心的可靠生物标志物。
