Pasloske K, Burger J, Conlon P
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph.
Can J Vet Res. 1998 Jul;62(3):237-40.
Ketorolac tromethamine (Toradol) is a relatively new, potent, non-narcotic analgesic with cyclooxygenase (COX) inhibitory activity and has been associated with gastric and renal toxicity in people and dogs. The objectives of this study were to establish whether endogenous PGE2 exists in the plasma of healthy dogs and to determine if, and to what magnitude, ketorolac alters PGE2 plasma concentrations after administration. Enzyme immunoassay measurement of a stable PGE2 derivative, bicyclo PGE2, showed that after i.v. administration of 0.5 mg/kg ketorolac tromethamine, 1 and 24 h plasma samples contained significantly (P < or = 0.01) less PGE2 than did plasma samples collected from dogs before the drug treatment. After p.o. administration, 1 h plasma samples contained significantly (P < or = 0.01) less PGE2 than did pretreatment samples, and the 24 h post-drug administration samples contained significantly (P < or = 0.01) less plasma PGE2 than the 96 h plasma samples. The results of this study suggest that a clinically effective single i.v. or p.o. dose of ketorolac tromethamine to healthy dogs causes a significant but reversible decrease in endogenous PGE2 production which may partially explain the drug's low therapeutic index.
酮咯酸氨丁三醇(痛力克)是一种相对较新的强效非麻醉性镇痛药,具有环氧化酶(COX)抑制活性,在人和犬中均与胃和肾毒性相关。本研究的目的是确定健康犬血浆中是否存在内源性前列腺素E2(PGE2),并确定酮咯酸给药后是否会改变以及在何种程度上改变血浆PGE2浓度。对一种稳定的PGE2衍生物双环PGE2进行酶免疫分析测定,结果显示,静脉注射0.5mg/kg酮咯酸氨丁三醇后,1小时和24小时的血浆样本中PGE2含量显著低于给药前采集的犬血浆样本(P≤0.01)。口服给药后,1小时的血浆样本中PGE2含量显著低于给药前样本(P≤0.01),给药后24小时的血浆样本中PGE2含量显著低于给药后96小时的血浆样本(P≤0.01)。本研究结果表明,对健康犬静脉注射或口服临床有效剂量的酮咯酸氨丁三醇会导致内源性PGE2生成显著但可逆性降低,这可能部分解释了该药物较低的治疗指数。