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Kidney weights were increased in both species but histological correlates were only observed in monkeys (tubular degeneration/regeneration [mainly diffuse], and interstitial oedema in the medulla were observed in both studies; there was no evidence of tubular necrosis). Increases in blood urea were observed in the 4 week monkey study which may have been associated with effects on the kidney and/or an anti-anabolic effect (due to a reduction in protein synthesis). The NOEL for kidney lesions was 5 mg/kg/day orally (PO) (ERAUC 0.8). Given the low safety margin, there is a potential for renal effects in patients treated for rosacea at the proposed dose. In rats, additional organs affected by doxycycline treatment include the adrenals (increased incidence of minimal cortical lipidosis) and, in the 6 month study only, the pharynx (minimal inflammatory cell infiltrate), while the spleen (reduction in the incidence of extramedullary haematopoiesis) was only affected at 600 mg/kg/day PO. Red blood cells were also affected in both studies in rats, with reductions in red cell numbers, and associated parameters (haemoglobin and haematocrit). The reduction in the incidence of extramedullary haematopoiesis in the spleen may have contributed to this finding at 600 mg/kg/day but red cell parameters were also reduced at lower doses (≥200 mg/kg/day). The NOEL for all of these effects was 20 mg/kg/day (ERAUC 1.7). |

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兩個物種的腎臟重量均增加,但組織學相關僅在猴子身上觀察到,(管狀退化/再生[主要擴散形式]和在兩個研究中均觀察到髓質間質的水腫;無腎小管壞死跡象)。在4周的猴子研究中觀察到血尿素升高,也是與腎臟和或抑制合成作用(由于蛋白質合成減少)有關。病變腎臟的未見作用劑量NOEL是5mg/kg/day口服?紤]到安全系數(shù)低,在建議劑量下對治療紅斑痤瘡患者有腎臟作用影響。 在小鼠中,多西環(huán)素治療影響其他器官包括腎上腺(增加最低皮質脂沉積風險),僅在6個月的研究中,咽(極少炎癥細胞滲入),然而脾臟(減少髓外造血功能風險)在口服600mg/kg/day時候受影響。血紅細胞在兩個小鼠研究中都受影響,造成紅細胞和相關指數(shù)(血紅蛋白和分血器計數(shù))減少。脾臟中髓外造血作用發(fā)生率減少在600mg/kg/day時顯著,但紅細胞指數(shù)在低劑量(≥200 mg/kg/day)也會降低。所有作用的未見作用劑量NOEL是20 mg/kg/day |
至尊木蟲 (知名作家)
Translator and Proofreader
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基于2樓做些修正(只做必需的改正,不包括語言): 兩個物種的腎臟重量均增加,但組織學相關僅在猴子身上觀察到,(【腎小管變性】/再生[主要擴散形式]和在兩個研究中均觀察到髓質間質的水腫;無腎小管壞死跡象)。在4周的猴子研究中觀察到血尿素升高,也是與腎臟和或抑制合成作用(由于蛋白質合成減少)有關。病變腎臟的未見作用劑量NOEL是5mg/kg/day口服?紤]到【低安全限度】,在建議劑量下對治療紅斑痤瘡患者有腎臟作用影響。 在【大鼠】中,多西環(huán)素治療影響其他器官包括腎上腺(增加最低皮質脂沉積風險),僅在6個月的研究中,咽(極少炎癥細胞滲入),然而脾臟(減少髓外造血功能風險)在口服600mg/kg/day時候受影響。【紅細胞】在兩個小鼠研究中都受影響,造成紅細胞和相關【參數(shù)】(血紅蛋白和【紅細胞壓積】)減少。脾臟中髓外造血作用發(fā)生率減少在600mg/kg/day時顯著,但紅細胞【參數(shù)】在低劑量(≥200 mg/kg/day)也會降低。所有作用的未見作用劑量NOEL是20 mg/kg/day 注:功勞在2樓,不要獎勵我 |
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