Irsigler K, Kritz H, Regal H, Kaspar L
Wien Klin Wochenschr. 1979 Jan 19;91(2):59-65.
An investigation was carried out on 30 diabetic patients in an attempt to clarify the relationship between serum biguanide levels and raised lactate. No consistent relationship was demonstrable between the serum biguanide level, administered dosage and time of administration. There was also no correlation between biguanide and lactate increase. It is not justifiable to quote a specific serum level of biguanides in defining lactic acidosis. A causal association between biguanide medication and lactic acidosis seems to be possible only by determination of serum and tissue levels. Determination of biguanide levels was carried out in the serum and tissue of a patient who had died as a result of lactic acidosis after phenformin administration. While the serum levels were only slightly higher than the therapeutic range, both liver and kidney tissue showed highly toxic levels. Furthermore, the amount of biguanides in the body was calculated in another patient successfully treated for lactic acidosis after buformin therapy. A differentiation should be made between biguanide-induced and biguanide-associated lactic acidosis. In both forms serum levels can be within relatively low ranges. In the former condition, the biguanides alone are responsible for the development of lactic acidosis by blocking the respiratory chain. In the latter condition they aggravate an already existing pathological condition, and can, therefore, represent a lethal factor.
对30名糖尿病患者进行了一项调查,以阐明血清双胍类药物水平与乳酸升高之间的关系。血清双胍类药物水平、给药剂量和给药时间之间未显示出一致的关系。双胍类药物与乳酸升高之间也没有相关性。在定义乳酸性酸中毒时引用特定的血清双胍类药物水平是不合理的。只有通过测定血清和组织水平,双胍类药物治疗与乳酸性酸中毒之间的因果关系似乎才有可能确定。对一名在服用苯乙双胍后因乳酸性酸中毒死亡的患者的血清和组织进行了双胍类药物水平测定。虽然血清水平仅略高于治疗范围,但肝脏和肾脏组织均显示出高毒性水平。此外,还计算了另一名在服用丁双胍治疗后成功治疗乳酸性酸中毒的患者体内双胍类药物的含量。应区分双胍类药物引起的和双胍类药物相关的乳酸性酸中毒。在这两种形式中,血清水平都可能处于相对较低的范围内。在前一种情况下,双胍类药物单独通过阻断呼吸链导致乳酸性酸中毒的发生。在后一种情况下,它们会加重已有的病理状况,因此可能是一个致命因素。