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首页> 外文期刊>Xenobiotica: the fate of foreign compounds in biological systems >Effect of inhalation exposure to toluene on the activity of organic anion transporting polypeptide (Oatp) using pravastatin as a probe drug in rats
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Effect of inhalation exposure to toluene on the activity of organic anion transporting polypeptide (Oatp) using pravastatin as a probe drug in rats

机译：吸入暴露对甲苯对大鼠探针药物在大鼠探针药物中有机阴离子输送多肽（OATP）活性的影响

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ABSTRACT: 1.?Toluene, used as a pure substance or in solvent mixtures, is the cause of occupational exposures of large numbers of workers in the world. The organic anion transporting polypeptides (OATP: human; Oatp: rodents) are drug carriers which have been frequently associated to drug–drug interactions. The objective of this study was to evaluate the influence of inhalation exposure to toluene in Oatp in vivo activity using pravastatin as a probe drug in rats. 2.?Male Wistar rats ((n = 6 per sampling time) were exposed to 85 mg/m3 toluene by inhalation or air in a nose only exposure system for 6 h/d, 5 d/week during 4 weeks, in order to simulate the occupational exposure to toluene at level slightly above the occupational exposure limit proposed by the American Conference of Governmental Industrial Hygienists (ACGIH). After 4 weeks of exposure, animals received a single dose of 20 mg/kg pravastatin orally. 3.?Areas under concentration × time curves extrapolated to infinite (AUC0–∞) were calculated by Gauss Laguerre quadrature. Non-exposed animals showed AUC0–∞ of 726.0 (261.8) ng h/mL for pravastatin and rats exposed to toluene 85 mg/m3 showed AUC0–∞ of 681.8 (80.1) ng h/mL [data presented as mean (standard error of the mean)]. No significant difference was observed in pravastatin kinetic disposition between groups in terms of 95% confidence interval for the difference between means. 4.?Toluene exposure by inhalation did not change the in vivo activity of Oatp evaluated by pravastatin kinetic disposition in rats. ? 2017 Informa UK Limited, trading as Taylor & Francis Group.
机译：摘要：1 .?Toluene，用作纯物质或溶剂混合物，是世界上大量工人职业暴露的原因。有机阴离子输送多肽（OATP：人; OATP：啮齿动物）是经常与药物 - 药物相互作用相关的药物载体。本研究的目的是评估利用普伐他汀作为大鼠探针药物在体内活性中吸入对甲苯的影响。 2.当在4周内，通过吸入或在4周内，通过吸入或空气暴露于85mg / m 3甲苯暴露于85mg / m 3甲苯的动脉Wistar大鼠（（N = 6），以便模拟略高于美国政府工业卫生患者（ACGIH）提出的职业暴露限制的职业暴露。曝光4周后，动物口服均为20毫克/千克普拉维拉汀。3.？areas通过高斯Laguerre正交计算浓度×时间曲线推断为无限（AUC0-Ⅵ）。非暴露的动物显示出726.0（261.8）Ng H / ml的普伐他汀和暴露于甲苯的大鼠85mg / m 3的大鼠显示AUC0 -6 681.8（80.1）Ng H / ml [数据作为平均值（平均值的标准误差）]。在基团之间的普伐他汀动力学置位中没有显着差异，在95％的置信区间之间的手段之间的差异。4 。？吸入的甲苯暴露没有改变vi大鼠普伐他汀动力学分化评价OATP的VO活性。还2017年Informa UK Limited，贸易为泰勒＆弗朗西斯集团。

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