ABSORPTION, DISTRIBUTION AND TOXICITY OF IBUPROFEN
ABSORPTION, DISTRIBUTION AND TOXICITY OF IBUPROFEN
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DOI：
10.1016/0041-008x(69)90032-5
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发表时间：
1969-01-01
影响因子：
3.8
通讯作者：
MILLS, RFN
中科院分区：
文献类型：
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作者：
ADAMS, SS;BOUGH, RG;MILLS, RFN
在小鼠、大鼠和犬中研究了布洛芬（2-（4-异丁基苯基）丙酸，一种具有抗炎、镇痛和解热特性的非甾体药物）单次经口或胃肠外给药后的毒性，以及在大鼠和犬中研究了重复经口给药长达6个月后的毒性。伊维菌素诱导胃肠道病变，犬中的致溃疡性高于大鼠;种属敏感性差异很可能与药物在犬血浆中的持久性更高有关。大鼠中发生的器官重量变化与组织学异常无关，并且在停止给药时逆转。对大鼠和兔有毒性的剂量没有胚胎毒性或致畸活性，尽管布洛芬或其代谢产物进入胎儿循环。在大鼠、家兔和犬中，口服给药的伊曲康快速吸收。大鼠体内的吸收主要发生在肠道，胃中的吸收程度较低，但也很显著。在兔血浆中检测到布洛芬的4种代谢产物，其中3种也在大鼠血浆中检测到，但在犬血浆中未检测到。布洛芬-14 C的分布研究表明，大鼠重复经口给药导致肾上腺、卵巢、甲状腺、皮肤和脂肪中的放射性蓄积，而结构或功能不受影响。然而，狗只在胆汁中有高水平。
The toxicity of ibuprofen, 2-(4-isobutylphenyl)propionic acid, a nonsteroidal agent with anti-inflammatory, analgesic, and antipyretic properties, was investigated in mice, rats, and dogs after single-dose oral or parenteral administration, and in rats and dogs after repeated oral administration for periods of up to 6 months. Ibuprofen induced gastrointestinal lesions, being more ulcerogenic in dogs than in rats; this difference in species susceptibility may well be related to the drug being more persistent in dog plasma. Organ weight changes occurring in rats were not associated with histologic abnormalities and were reversed when dosing ceased. Doses toxic to rats and rabbits were devoid of embryotoxic or teratogenic activity though ibuprofen or its metabolites entered the fetal circulation. Ibuprofen administered orally was rapidly absorbed in rats, rabbits, and dogs. Absorption in rats was shown to occur mainly from the intestine and to a lesser, though significant, extent from the stomach. Four metabolites of ibuprofen were detected in rabbit plasma, 3 of these also in rat plasma, but none in dog plasma. Distribution studies with ibuprofen-14C revealed that repeated oral dosing of rats led to some accumulation of radioactivity in the adrenals, ovaries, thyroid, skin, and fat, without structure or function being affected. Dogs, however, had high levels only in bile.