Dine T, Luyckx M, Gressier B, Brunet C, Souhait J, Nogarede S, Vanpoucke J, Courbon F, Plusquellec Y, Houin G
Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques, 3 rue du Professeur Laguesse BP83, F59006 Cedex, Lille, France.
Med Eng Phys. 2000 Apr;22(3):157-65. doi: 10.1016/s1350-4533(00)00022-9.
The degree of exposure to DEHP was assessed in 11 patients with chronic renal failure undergoing maintenance haemodialysis. The amount of DEHP leached from the dialyser during a 4-h dialysis session was estimated by monitoring the DEHP blood concentration using a HPLC method. When a patient undergoes a dialysis treatment, the concentration of di-2-ethylhexyl phthalate (DEHP) in venous blood is increased when the blood crosses through the dialysis apparatus. This increase may be explained either because DEHP is not extracted by the dialyser or because DEHP comes from the dialysis bath due to contact of blood against plasticized pipes. To explain the increasing concentration of DEHP during treatment of renal failure using plasticized tubing, we propose a pharmacokinetic compartmental model in order to fit raw data obtained from dialysed patients and to get the amount of DEHP which enters the body by AUC calculations. Results obtained after HPLC analysis show a high degree of interpatient variability in DEHP retained. This amount can reach a toxicity level because of repetitive dialysis treatments over prolonged periods of time. In the coming years, it seems necessary to reconsider the use of DEHP as a plasticizer in medical devices. Highly unacceptable amounts of DEHP leached during the dialysis session could be easily avoided by careful selection of haemodialysis tubing.
对11例接受维持性血液透析的慢性肾衰竭患者的邻苯二甲酸二（2-乙基己基）酯（DEHP）暴露程度进行了评估。通过使用高效液相色谱法监测DEHP血药浓度，估算了在4小时透析过程中透析器中浸出的DEHP量。当患者接受透析治疗时，血液通过透析装置时，静脉血中邻苯二甲酸二（2-乙基己基）酯（DEHP）的浓度会升高。这种升高可能是因为透析器未提取DEHP，或者是因为血液与增塑管接触，DEHP来自透析液。为了解释使用增塑管治疗肾衰竭期间DEHP浓度的升高，我们提出了一个药代动力学房室模型，以便拟合从透析患者获得的原始数据，并通过曲线下面积（AUC）计算得出进入体内的DEHP量。高效液相色谱分析得到的结果显示，患者之间DEHP残留量存在高度差异。由于长时间重复透析治疗，这个量可能会达到毒性水平。在未来几年，似乎有必要重新考虑在医疗器械中使用DEHP作为增塑剂。通过仔细选择血液透析管，可以很容易地避免透析过程中浸出的DEHP量达到高度不可接受的程度。
