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慢性透析患者必需氨基酸的药代动力学

Pharmacokinetics of essential amino acids in chronic dialysis-patients.

作者信息

Chami J, Reidenberg M M, Wellner D, David D S, Rubin A L, Stenzel K H

出版信息

Am J Clin Nutr. 1978 Sep;31(9):1652-9. doi: 10.1093/ajcn/31.9.1652.

Abstract

Possible disorders of essential amino acid (EAA) metabolism in maintenance dialysis patients (D) were studied by measuring plasma amino acids before and sequentially after administering a mixture of 8 EAA po and iv. The EAA were in a ratio similar to that required for optimal utilization, and the total dose given was within physiological range. Ten D and six normals (N) received 150 mg/kg po as a 10.5 g/dl solution and 117 mg/kg iv as a 5.1 g/dl solution infused at a constant rate of mg/kg per min. Blood glucose and immunoreactive insulin were also measured. Both D and N were postabsorptive and at least 18 hr postdialysis. The fraction of the oral dose appearing in the systemic circulation was variable for each EAA in both N and D. Total body clearance was significantly lower in D (P less than 0.05) for theronine, phenylalanine, valine, leucine, and isoleucine, and this difference could not be explained by changes in renal excretion. The apparent volume of distribution did not differ between N and D for all EAA except for valine and phenylalanine. Blood glucose insulin varied only slightly in both N and D for all EAA except for valine and phenylalanine. Blood glucose and insulin varied only slightly in both N and D. These studies indicate that there are a variety of significant abnormalities in the metabolism of specific EAA in D. Decreased total body clearance of the branched-chain amino acids, since they are primarily metabolized total body clearance of the brnached-chain amino acids, since they are primarily metabolized by muscle, may result from a defect in muscle metabolism in D.

摘要

通过在口服和静脉注射8种必需氨基酸混合物之前和之后依次测量血浆氨基酸,研究了维持性透析患者(D)必需氨基酸(EAA)代谢的可能紊乱情况。这些必需氨基酸的比例与最佳利用所需的比例相似,给予的总剂量在生理范围内。10名透析患者(D)和6名正常人(N)接受了口服150mg/kg的10.5g/dl溶液,并以每分钟mg/kg的恒定速率静脉注射117mg/kg的5.1g/dl溶液。还测量了血糖和免疫反应性胰岛素。D组和N组均处于吸收后状态且至少在透析后18小时。在N组和D组中,每种必需氨基酸出现在体循环中的口服剂量分数都是可变的。对于苏氨酸、苯丙氨酸、缬氨酸、亮氨酸和异亮氨酸,D组的全身清除率显著降低(P<0.05),这种差异无法用肾脏排泄的变化来解释。除缬氨酸和苯丙氨酸外,所有必需氨基酸在N组和D组中的表观分布容积没有差异。除缬氨酸和苯丙氨酸外,所有必需氨基酸在N组和D组中的血糖胰岛素仅略有变化。N组和D组的血糖和胰岛素变化都很小。这些研究表明,D组特定必需氨基酸的代谢存在多种显著异常。支链氨基酸的全身清除率降低,因为它们主要在全身代谢,支链氨基酸的全身清除率降低,因为它们主要由肌肉代谢,这可能是由于D组肌肉代谢缺陷所致。

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