吉非贝齐对红细胞氧运输特性的影响。

Effects of gemfibrozil on the oxygen transport properties of erythrocytes.

Scatena R, Nocca G, Messana I, De Sole P, Baroni S, Zuppi C, Castagnola M, Giardina B

Institute of Chemistry and Clinical Chemistry, Faculty of Medicine, Catholic University, Rome, Italy.

Br J Clin Pharmacol. 1995 Jan;39(1):25-30. doi: 10.1111/j.1365-2125.1995.tb04405.x.

Abstract

In the present study we have investigated the effects of the relatively low plasma concentrations of gemfibrozil (GFZ) found in clinical practice on the oxygen dissociation curve (ODC) of erythrocytes. 2. ODCs were measured at 30 degrees C and 37 degrees C and at pH 7.4: a) both on HbA solution and erythrocytes incubated in vitro with gemfibrozil and clofibric acid; b) on erythrocytes from healthy volunteers treated with a single oral dose of gemfibrozil. 3. These experiments showed a significant drug-induced shift of the ODC towards lower O2 affinity values without any significant modification of metabolic parameters of erythrocytes such as intracellular pH and intraerythrocytic levels of ATP and DPG. 4. In our experimental conditions gemfibrozil appears to lower both in vitro and in vivo, the partial pressure of oxygen required to give 50% of the haemes saturated with oxygen (P50) of erythrocytes from the control value of 24 +/- 0.5 mm Hg to 29 +/- 0.5 mm Hg (mean +/- s.d.; P < 0.02 by ANOVA). 5. These data clearly indicate that therapeutic doses of gemfibrozil may influence the oxygen transport properties of red cells. This effect could have relevant pharmacological and toxicological implications.

摘要

在本研究中，我们调查了临床实践中发现的相对较低血浆浓度的吉非贝齐（GFZ）对红细胞氧解离曲线（ODC）的影响。2. 在30℃和37℃以及pH 7.4条件下测量ODC：a）对在体外与吉非贝齐和氯贝酸一起孵育的血红蛋白A溶液和红细胞进行测量；b）对单次口服吉非贝齐治疗的健康志愿者的红细胞进行测量。3. 这些实验表明，药物诱导ODC显著向较低的氧亲和力值偏移，而红细胞的代谢参数如细胞内pH以及细胞内ATP和DPG水平没有任何显著改变。4. 在我们的实验条件下，吉非贝齐在体外和体内似乎都能降低使50%的血红素与氧饱和所需的氧分压（P50），红细胞的P50从对照值24±0.5毫米汞柱降至29±0.5毫米汞柱（平均值±标准差；方差分析P<0.02）。5. 这些数据清楚地表明，治疗剂量的吉非贝齐可能会影响红细胞的氧运输特性。这种效应可能具有相关的药理学和毒理学意义。