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2-丁氧基乙醇在人体志愿者中的经皮吸收与代谢:一项微透析研究。

Percutaneous absorption and metabolism of 2-butoxyethanol in human volunteers: a microdialysis study.

作者信息

Korinth Gintautas, Jakasa Ivone, Wellner Tanja, Kezic Sanja, Krüse Jacob, Schaller Karl Heinz

机构信息

Institute and Out-Patient Clinic of Occupational, Social and Environmental Medicine, University Erlangen-Nuremberg, Schillerstrasse 25/29, D-91054 Erlangen, Germany.

出版信息

Toxicol Lett. 2007 Apr 25;170(2):97-103. doi: 10.1016/j.toxlet.2007.01.013. Epub 2007 Feb 11.

Abstract

We determined percutaneous absorption kinetics of 2-butoxyethanol (BE) in volunteers using microdialysis. Four male volunteers were dermally exposed twice to 90% and 50% aqueous solutions (v/v) of BE for 4.5h. To determine percutaneous absorption kinetics the concentration of BE was measured in the dialysate samples collected at 30 min-intervals throughout exposure. The systemic absorption, which is needed to determine recovery of the BE in the dialysate, was estimated from the concentration of the main metabolite of BE, free butoxyacetic acid (BAA) in urine. A pseudo steady-state percutaneous absorption was reached approximately at 2h of exposure for both BE concentrations. The maximum dermal flux of 50% BE was higher than that of 90% BE (2.8+/-0.4, 1.9+/-0.6 mg cm(-2)h(-1), respectively). The more diluted BE solution showed shorter lag time: 25 min versus 39 min. The amount of BAA was determined in the pooled dialysate samples collected at 4 and 4.5h. The dermal metabolism seems to be low, the BAA amount ranged from 0.03% to 1.9% of the BE in the same dialysate. Our study demonstrates applicability of microdialysis technique for assessment of percutaneous absorption kinetics and dermal metabolism without interference from the systemic compartment.

摘要

我们使用微透析技术测定了志愿者皮肤对2-丁氧基乙醇(BE)的吸收动力学。4名男性志愿者皮肤分别两次暴露于90%和50%(v/v)的BE水溶液中,持续4.5小时。为了测定经皮吸收动力学,在整个暴露过程中每隔30分钟收集透析液样本,测定其中BE的浓度。从尿液中BE的主要代谢产物游离丁氧基乙酸(BAA)的浓度估算全身吸收情况,这对于确定透析液中BE的回收率是必要的。对于两种BE浓度,大约在暴露2小时时达到假稳态经皮吸收。50% BE的最大皮肤通量高于90% BE(分别为2.8±0.4、1.9±0.6 mg·cm⁻²·h⁻¹)。稀释度更高的BE溶液滞后时间更短:分别为25分钟和39分钟。在4小时和4.5小时收集的合并透析液样本中测定BAA的量。皮肤代谢似乎较低,在同一透析液中BAA的量占BE的0.03%至1.9%。我们的研究证明了微透析技术在评估经皮吸收动力学和皮肤代谢方面的适用性,且不受全身循环的干扰。

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