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地高辛代谢产物在肾衰竭中的蓄积问题。

The question of cumulation of digoxin metabolites in renal failure.

作者信息

Gibson T P, Nelson H A

出版信息

Clin Pharmacol Ther. 1980 Feb;27(2):219-23. doi: 10.1038/clpt.1980.34.

DOI:10.1038/clpt.1980.34
PMID:7353343
Abstract

Using high-performance liquid chromatography (HPLC) to separate digoxin from its metabolites digoxigenin, digoxigenin-bis-digitoxoside, and digoxigenin-mono-digitoxoside with subsequent quantitation by 125I radioimmunoassay (RIA), we examined the plasma of patients on long-term oral digoxin therapy. Digoxin was also measured by RIA without prior HPLC separation. Nine patients requiring maintenance dialysis and 9 subjects with lesser degrees of renal impairment were studied. Trace amounts of 1 or more of the digoxin metabolites were found in the plasma of all dialysis patients while subjects with lesser degrees of renal failure had either none or only 1 metabolite in trace amounts. The ratio of HPLC digoxin without HPLC was 0.83 +/- 0.12 (SD) in renal failure patients and 1.06 +/- 0.09 in subjects with renal function (p less than 0.01). RIA overestimates the amount of digoxin in plasma of renal failure patients and in them from 6% to 42% of plasma digoxin, as determined by conventional 125I RIA, may represent compounds other than digoxin.

摘要

我们采用高效液相色谱法(HPLC)将地高辛与其代谢产物洋地黄毒苷、洋地黄毒苷双洋地黄毒糖甙及洋地黄毒苷单洋地黄毒糖甙分离,随后通过¹²⁵I放射免疫测定法(RIA)进行定量分析,以此检测长期接受口服地高辛治疗患者的血浆。地高辛也在未经HPLC分离的情况下通过RIA进行测量。研究对象包括9例需要维持性透析的患者以及9例肾功能损害程度较轻的受试者。在所有透析患者的血浆中均发现痕量的1种或多种地高辛代谢产物,而肾功能损害程度较轻的受试者则未检测到或仅检测到痕量的1种代谢产物。肾功能衰竭患者中经HPLC测定的地高辛与未经HPLC测定的地高辛之比为0.83±0.12(标准差),肾功能正常的受试者该比值为1.06±0.09(p<0.01)。RIA高估了肾功能衰竭患者血浆中的地高辛含量,按照传统¹²⁵I RIA测定,其中6%至42%的血浆地高辛可能代表除地高辛以外的化合物。

相似文献

1
The question of cumulation of digoxin metabolites in renal failure.地高辛代谢产物在肾衰竭中的蓄积问题。
Clin Pharmacol Ther. 1980 Feb;27(2):219-23. doi: 10.1038/clpt.1980.34.
2
Quantitation of digoxigenin in serum following oral administration of digoxin in humans.人体口服地高辛后血清中洋地黄毒苷的定量分析。
Res Commun Chem Pathol Pharmacol. 1977 Jul;17(3):497-506.
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Clin Pharmacol Ther. 1982 Jun;31(6):695-704. doi: 10.1038/clpt.1982.98.
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Biotransformation and elimination of digoxin with normal and minimal renal function.地高辛在肾功能正常和轻度受损时的生物转化与消除。
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Variable cross-reactivity of digoxin metabolites in digoxin immunoassays.地高辛免疫测定中地高辛代谢物的可变交叉反应性。
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Studies on digitalis. V. The influence of impaired renal function, hemodialysis, and drug interaction on serum protein binding of digitoxin and digoxin.洋地黄研究。V. 肾功能损害、血液透析及药物相互作用对洋地黄毒苷和地高辛血清蛋白结合率的影响。
Clin Pharmacol Ther. 1976 Jul;20(1):6-14. doi: 10.1002/cpt19762016.
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False-positive digoxin measurements due to conjugated metabolite accumulation in combined renal and hepatic dysfunction.在合并肾和肝功能不全时,由于结合代谢产物蓄积导致地高辛测量结果出现假阳性。
Am J Nephrol. 1987;7(5):355-9. doi: 10.1159/000167501.

引用本文的文献

1
The bioavailability of digoxin from three oral formulations measured by a specific h.p.l.c. assay.通过特定的高效液相色谱法测定的三种口服制剂中地高辛的生物利用度。
Br J Clin Pharmacol. 1993 Feb;35(2):136-42. doi: 10.1111/j.1365-2125.1993.tb05679.x.
2
Evidence of nonlinearity in digoxin pharmacokinetics.
J Pharmacokinet Biopharm. 1981 Apr;9(2):147-66. doi: 10.1007/BF01068079.
3
Drug metabolites in renal failure: pharmacokinetic and clinical implications.肾衰竭中的药物代谢产物:药代动力学及临床意义
Clin Pharmacokinet. 1981 Sep-Oct;6(5):329-45. doi: 10.2165/00003088-198106050-00001.
4
Increased metabolism to dihydrodigoxin after intake of a microencapsulated formulation of digoxin.摄入地高辛微囊制剂后二氢地高辛的代谢增加。
Eur J Clin Pharmacol. 1984;27(2):197-202. doi: 10.1007/BF00544045.
5
Clinical pharmacokinetics of cardiac glycosides in patients with renal dysfunction.肾功能不全患者中强心苷类药物的临床药代动力学
Clin Pharmacokinet. 1983 Mar-Apr;8(2):155-78. doi: 10.2165/00003088-198308020-00003.
6
Interpretation of drug levels in acute and chronic disease states.急性和慢性疾病状态下药物水平的解读
Clin Pharmacokinet. 1985 Nov-Dec;10(6):498-513. doi: 10.2165/00003088-198510060-00003.
7
Digitalis. An update of clinical pharmacokinetics, therapeutic monitoring techniques and treatment recommendations.洋地黄。临床药代动力学、治疗监测技术及治疗建议的最新进展。
Clin Pharmacokinet. 1988 Sep;15(3):165-79. doi: 10.2165/00003088-198815030-00002.