Jones C A, Conybeare G, Mortensen A, Catto L C, Atterwill C K
Smith Kline & French Research Ltd., Welwyn, Herts, UK.
J Pharm Pharmacol. 1989 Jan;41(1):68-71. doi: 10.1111/j.2042-7158.1989.tb06335.x.
This study was designed to establish whether SK&F 93574 releases histamine in dogs. Three female beagle dogs each received single infusions (on separate days) of each of SK&F 93574 (2.5 mg kg-1), polyvinylpyrrolidone (PVP, 20 mg kg-1) and sterile saline. The treatments were given at 14 day intervals by rapid intravenous infusion at 0.5 mL kg-1 min-1 for 2 minutes. Dogs showed clinical signs of histamine release such as vasodilation, licking lips, head drooping and increased gut movement after treatment with the known histamine releaser PVP or the test compound SK&F 93574. These signs were of similar severity and duration for the two compounds. No such changes were observed when the dogs received vehicle alone. Treatment with PVP or SK&F 93574 also resulted in markedly elevated plasma histamine concentrations (greater than 10-fold increase over control). It is concluded that intravenous administration of SK&F 93574 to dogs is associated with histamine release.
本研究旨在确定SK&F 93574是否会在犬类中释放组胺。三只雌性比格犬分别在不同日期接受了单次输注,分别为SK&F 93574(2.5毫克/千克)、聚乙烯吡咯烷酮(PVP,20毫克/千克)和无菌生理盐水。每隔14天进行一次治疗,以0.5毫升/千克·分钟的速度快速静脉输注2分钟。在用已知的组胺释放剂PVP或受试化合物SK&F 93574治疗后,犬类出现了组胺释放的临床症状,如血管扩张、舔唇、头部下垂和肠道蠕动增加。两种化合物的这些症状严重程度和持续时间相似。当犬只单独接受赋形剂时,未观察到此类变化。用PVP或SK&F 93574治疗也导致血浆组胺浓度显著升高(比对照组增加超过10倍)。得出的结论是,给犬静脉注射SK&F 93574与组胺释放有关。