Burdmann E A, Andoh T F, Rosen S, Lindsley J, Munar M Y, Elzinga L W, Bennett W M
Division of Nephrology, Hypertension and Clinical Pharmacology, Oregon Health Sciences University, Portland.
Kidney Int. 1994 Mar;45(3):684-91. doi: 10.1038/ki.1994.92.
Cyclosporin G (CsG) is an analogue of cyclosporin A (CsA) with strong immunosuppressive activity. We compared these two drugs in a rat model in which salt depletion promotes irreversible renal interstitial fibrosis with renal dysfunction in animals given CsA for three weeks. When both drugs were given in the same dosage on a weight basis (15 mg/kg/day, subcutaneously), CsA blood levels were higher than CsG (3305 vs. 1824 ng/ml, P < 0.001). This could be explained by a higher CsG clearance (6.4 vs. 4.3 ml/min/kg in CsA, P < 0.0001) resulting in smaller CsG area under the curve. There was also lower renal and hepatic CsG tissue concentrations. CsA induced a dramatic decrease in GFR, 0.14 in CsA versus 0.67 ml/min/100 g in control, P < 0.001, and increased urinary excretion of N-acetyl beta-D-glucosaminidase (NAG), 21 in CsA versus 13 IU/gCr in control rats, P < 0.001. CsG-treated and control rats had similar GFR and urinary NAG. When CsA dosage was decreased to 7.5 mg/kg blood levels were similar to those found with CsG 15 mg/kg. CsA at this dose caused a reduced GFR (0.29 ml/min/100 g) and an increased urinary NAG (20 IU/gCr) (P < 0.01 vs. control for both). Both dosages of CsA induced considerable cortical and medullary injury (interstitial fibrosis and tubular atrophy), more severe than the histological damage found in CsG-treated rats. Neither drug promoted significant changes in liver function or histology.(ABSTRACT TRUNCATED AT 250 WORDS)
环孢素G（CsG）是环孢素A（CsA）的类似物，具有很强的免疫抑制活性。我们在一个大鼠模型中比较了这两种药物，在该模型中，盐耗竭会促进给予CsA三周的动物出现不可逆的肾间质纤维化并伴有肾功能障碍。当两种药物按体重给予相同剂量（15mg/kg/天，皮下注射）时，CsA的血药浓度高于CsG（3305对1824ng/ml，P<0.001）。这可以用CsG更高的清除率来解释（CsA为4.3ml/min/kg，CsG为6.4ml/min/kg，P<0.0001），导致CsG的曲线下面积更小。肾和肝组织中的CsG浓度也较低。CsA导致肾小球滤过率（GFR）显著下降，CsA组为0.14，对照组为0.67ml/min/100g，P<0.001，并且N-乙酰-β-D-氨基葡萄糖苷酶（NAG）的尿排泄增加，CsA组为21，对照组大鼠为13IU/gCr，P<0.001。CsG治疗组大鼠和对照组大鼠的GFR及尿NAG相似。当CsA剂量降至7.5mg/kg时，血药浓度与15mg/kg CsG时相似。此剂量的CsA导致GFR降低（0.29ml/min/100g）和尿NAG增加（20IU/gCr）（两者与对照组相比P<0.01）。两种剂量的CsA均引起相当程度的皮质和髓质损伤（间质纤维化和肾小管萎缩），比CsG治疗组大鼠的组织学损伤更严重。两种药物均未引起肝功能或组织学的显著变化。（摘要截短于250字）
