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| Animal:human exposure ratios (based on AUC; ERAUC) achieved in the repeat dose toxicity studies were adequate in rats, reaching up to 11 in the 6 month study but somewhat low in Cynomolgus monkeys (up to 2.5 in the 1 year study). It is unclear why AUC values in the 1 year monkey study were considerably lower than those at the same or similar doses in the 4 week study. Plasma samples from both studies were analysed by the same laboratory using the same (or closely similar) methodology, but inter-animal variability was high. |

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| 在重復(fù)劑量毒性研究中,已在大鼠中取得了足夠的動(dòng)物:人曝光比(基于AUC; ERAUC),在6個(gè)月的研究中高達(dá)11,但在食蟹猴中稍低(在1年的研究中最多為2.5)。現(xiàn)在還不清楚為什么在1年猴研究中AUC值明顯低于用相同或相似劑量進(jìn)行的4周研究。用相同(或大致相同)的方法在同一實(shí)驗(yàn)室分析了兩項(xiàng)血漿樣品,但動(dòng)物間變異性高。 |
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