Hepatic clearance, but not gut availability, of erythromycin is altered in patients with end-stage renal disease.
Hepatic clearance, but not gut availability, of erythromycin is altered in patients with end-stage renal disease.
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DOI：
10.1038/clpt.2009.247
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发表时间：
2010-04
影响因子：
6.7
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中科院分区：
文献类型：
--
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终末期肾病（ESRD）患者的药物非肾清除率明显低于肾功能正常的患者。使用红霉素（ER）作为探针化合物，我们研究了非肾清除率的降低是否由于肝清除率（CLH）和/或肠道代谢的减少。我们还研究了尿毒症毒素3 -羧基- 4 -甲基- 5 -丙基- 2 -呋喃丙酸（CMPF）和硫酸吲哚酚（Indox）对内质网处置的潜在影响。在口服（250 mg）和静脉（125 mg）给药后，对12名ESRD患者和12名健康对照进行了路线随机、双向交叉的ER药代动力学研究。在ESRD患者中，clh相对于基线值下降了31%(0.35±0.14 l/h/kg vs. 0.51±0.13 l/h/kg，P= 0.01)，稳态分布体积没有变化。口服给药时，ESRD患者内质网的生物利用度增加了36%，而且这种增加与肠道利用度的变化无关。正如预期的那样，患者血浆中CMPF和Indox水平明显高于健康对照组。然而，CLHof ER与尿毒症毒素水平之间没有相关性。临床药理学与治疗学（2010）874,465-472。doi: 10.1038 / clpt.2009.247
Nonrenal clearance of drugs can be significantly lower in patients with end‐stage renal disease (ESRD) than in those with normal renal function. Using erythromycin (ER) as a probe compound, we investigated whether this decrease in nonrenal clearance is due to reduced hepatic clearance (CLH) and/or gut metabolism. We also examined the potential effects of the uremic toxins 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furan propanoic acid (CMPF) and indoxyl sulfate (Indox) on ER disposition. Route‐randomized, two‐way crossover pharmacokinetic studies of ER were conducted in 12 ESRD patients and 12 healthy controls after oral (250 mg) and intravenous (125 mg) dosing with ER. In patients with ESRD, CLHdecreased 31% relative to baseline values (0.35 ± 0.14 l/h/kg vs. 0.51 ± 0.13 l/h/kg,P= 0.01), with no change in steady‐state volume of distribution. With oral dosing, the bioavailability of ER increased 36% in patients with ESRD, and this increase was not related to changes in gut availability. As expected, plasma levels of CMPF and Indox were significantly higher in the patients than in the healthy controls. However, no correlation was observed between CLHof ER and the levels of uremic toxins.Clinical Pharmacology & Therapeutics(2010)874, 465–472. doi:10.1038/clpt.2009.247
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