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接受持续性非卧床腹膜透析治疗患者中浸出的邻苯二甲酸二(2-乙基己基)酯的转归

The fate of leached di(2-ethylhexyl)phthalate in patients undergoing CAPD treatment.

作者信息

Mettang T, Thomas S, Kiefer T, Fischer F P, Kuhlmann U, Wodarz R, Rettenmeier A W

机构信息

Robert Bosch Hospital, Department of Internal Medicine, Stuttgart, Germany.

出版信息

Perit Dial Int. 1996 Jan-Feb;16(1):58-62.

PMID:8616175
Abstract

OBJECTIVES

To evaluate the degree of exposure to and the fate of di(2-ethylhexyl)phthalate (DEHP) and its major derivatives mono(2-ethylhexyl)phthalate (MEHP), 2-ethylhexanol (2-EH), and phthalic acid (PA) in patients undergoing regular continuous ambulatory peritoneal dialysis (CAPD) during a 4-hour dwell period.

DESIGN

Prospective, controlled.

SETTING

Teaching hospital, Department of Nephrology.

PARTICIPANTS

Seven elderly patients on stable CAPD using Fresenius instruments and dialysate and 6 age-matched healthy controls.

INTERVENTIONS

During a routinely performed peritoneal equilibration test (PET), blood and dialysate samples were drawn before and 120 and 240 min after the dwell was started. In addition, blood samples were taken from a group of volunteers participating in a pharmacological study.

MEASUREMENTS

Quantitative analysis of DEHP and its hydrolysis products was performed by selected ion-monitoring gas chromatography/mass spectrometry, operating the mass spectrometer in a combined positive and negative ion chemical ionization mode.

RESULTS

Serum concentrations of DEHP and PA were significantly higher in patients (median: 0.079 microgram/mL, range: 0.032-0.210 microgram/mL; and 0.167 microgram/mL, range: 0.097-0.231 microgram/mL, respectively) than in controls [0.0195 microgram/mL, range: 0.016-0.025 microgram/mL (p = 0.0027) and 0.0120 microgram/mL, range: 0.006-0.034 microgram/mL (p = 0.0026), respectively]. Concentration of MEHP in the fluid of CAPD bags prior to use was four times higher than that of the parent compound. During the first 4 hours of dwell time, the concentrations of MEHP and 2-EH in dialysate consistently decreased from 0.177 (range: 0.137-0.239 microgram/mL) to 0.022 microgram/mL (range: 0.005-0.058 microgram/mL) (p = 0.017), and from 0.087 (range: 0.075-0.097 microgram/mL) to 0.05 microgram/mL (range: 0.023-0.064 microgram/mL) (p = 0.017), respectively, while the concentration of DEHP remained stable. Remarkably high concentrations of PA (0.129 microgram/mL; range: 0.038-0.466 microgram/mL) were found in CAPD bags prior to use, and these concentrations tended to increase during dwell time, without statistical significance, however (0.135 microgram/mL; range: 0.073-0.659 microgram/mL, p = 0.062).

CONCLUSIONS

Patients on CAPD are regularly exposed to considerable amounts of phthalic ester derivatives, mainly to MEHP and PA. MEHP seems to be well absorbed by the peritoneal membrane. The long-term effects of this exposure remain to be elucidated.

摘要

目的

评估接受规律持续性非卧床腹膜透析(CAPD)的患者在4小时留腹期间邻苯二甲酸二(2-乙基己基)酯(DEHP)及其主要衍生物单(2-乙基己基)邻苯二甲酸酯(MEHP)、2-乙基己醇(2-EH)和邻苯二甲酸(PA)的暴露程度及转归情况。

设计

前瞻性对照研究。

地点

教学医院肾内科。

参与者

7例使用费森尤斯仪器和透析液进行稳定CAPD治疗的老年患者以及6例年龄匹配的健康对照者。

干预措施

在常规进行的腹膜平衡试验(PET)期间,留腹开始前、开始后120分钟和240分钟采集血液和透析液样本。此外,从一组参与药物研究的志愿者中采集血样。

测量方法

采用选择离子监测气相色谱/质谱联用技术,在质谱仪的正离子和负离子化学电离模式下对DEHP及其水解产物进行定量分析。

结果

患者血清中DEHP和PA的浓度显著高于对照组(中位数分别为:0.079微克/毫升,范围:0.032 - 0.210微克/毫升;以及0.167微克/毫升,范围:0.097 - 0.231微克/毫升),对照组分别为[0.0195微克/毫升,范围:0.016 - 0.025微克/毫升(p = 0.0027)和0.0120微克/毫升,范围:0.006 - 0.034微克/毫升(p = 0.0026)]。使用前CAPD袋中MEHP的浓度比母体化合物高4倍。在留腹的前4小时内,透析液中MEHP和2-EH的浓度持续下降,分别从0.177(范围:0.137 - 0.239微克/毫升)降至0.022微克/毫升(范围:0.005 - 0.058微克/毫升)(p = 0.017),以及从0.087(范围:0.075 - 0.097微克/毫升)降至0.05微克/毫升(范围:0.023 - 0.064微克/毫升)(p = 0.017),而DEHP的浓度保持稳定。使用前CAPD袋中PA的浓度显著较高(0.129微克/毫升;范围:0.038 - 0.466微克/毫升),且这些浓度在留腹期间有升高趋势,但无统计学意义(0.135微克/毫升;范围:0.073 - 0.659微克/毫升,p = 0.062)。

结论

CAPD患者经常接触大量邻苯二甲酸酯衍生物,主要是MEHP和PA。MEHP似乎能被腹膜很好地吸收。这种暴露的长期影响仍有待阐明。

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