Cook Margaret, Gustafson Daniel L, Kroeker Katie, Shropshire Sarah, Zersen Kristin M
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
J Vet Intern Med. 2025 Sep-Oct;39(5):e70221. doi: 10.1111/jvim.70221.
Grape-induced acute kidney injury (AKI) is caused by tartaric acid and may lead to death in dogs. Probenecid, an organic anion transporter-1 inhibitor, recently has been shown to block the uptake of tartaric acid in Madin-Darby canine kidney cells and has been suggested as a possible target for prevention of AKI after grape ingestion.
HYPOTHESIS/AIMS: Assess the safety and pharmacokinetics (PK) of PO probenecid in dogs. We hypothesized that probenecid would result in mild, self-limiting gastrointestinal (GI) adverse effects and would be safe in healthy dogs. Additionally, we hypothesized that PO probenecid (50 mg/kg) would have adequate bioavailability and achieve pharmacologically active plasma drug concentrations.
Six healthy beagle dogs.
Pharmacokinetic (PK) study. Dogs were given 50 mg/kg of probenecid PO, with PK data collected for 48 h after administration. Complete blood count, serum biochemistry profile, urinalysis, and clinical monitoring were performed throughout a 21-day study period to assess safety. Plasma concentration versus time data was analyzed using non-compartmental and two-compartmental modeling.
Orally administered probenecid had excellent estimated bioavailability (82.6%) and rapid absorption, with a mean maximal plasma concentration of 589.3 μM (range: 368.0-830.5 μM) within 1.5 h. The mean volume of distribution was 0.71 L/kg, with mean systemic clearance of 0.022 L/h/kg and mean half-life of 24.1 h. Probenecid was well tolerated by all six dogs, with no clinically relevant adverse effects noted.
Orally administered probenecid is safe and bioavailable in healthy dogs. Future clinical trials assessing PO probenecid in dogs with known tartaric acid ingestion are warranted.
葡萄诱发的急性肾损伤（AKI）由酒石酸引起，可导致犬类死亡。丙磺舒是一种有机阴离子转运体-1抑制剂，最近已证明其可阻断马-达二氏犬肾细胞对酒石酸的摄取，并被认为是预防葡萄摄入后AKI的一个可能靶点。
假设/目的：评估犬口服丙磺舒的安全性和药代动力学（PK）。我们假设丙磺舒会导致轻微的、自限性的胃肠道（GI）不良反应，且对健康犬是安全的。此外，我们假设口服丙磺舒（50mg/kg）具有足够的生物利用度，并能达到具有药理活性的血浆药物浓度。
6只健康的比格犬。
药代动力学（PK）研究。给犬口服50mg/kg丙磺舒，并在给药后48小时收集PK数据。在整个21天的研究期间进行全血细胞计数、血清生化分析、尿液分析和临床监测以评估安全性。使用非房室和二房室模型分析血浆浓度与时间的数据。
口服丙磺舒具有出色的估计生物利用度（82.6%）和快速吸收，在1.5小时内平均最大血浆浓度为589.3μM（范围：368.0 - 830.5μM）。平均分布容积为0.71L/kg，平均全身清除率为0.022L/h/kg，平均半衰期为24.1小时。所有6只犬对丙磺舒耐受性良好，未观察到临床相关的不良反应。
口服丙磺舒在健康犬中是安全且具有生物利用度的。有必要进行未来的临床试验，评估已知摄入酒石酸的犬口服丙磺舒的情况。
