Treatment of chronic congenital lactic acidosis by oral administration of dichloroacetate
Treatment of chronic congenital lactic acidosis by oral administration of dichloroacetate
复制标题
口服二氯乙酸治疗慢性先天性乳酸性酸中毒
DOI：
--
复制
发表时间：
1986
影响因子：
4.2
通讯作者：
K. Nishiyama
中科院分区：
文献类型：
--
作者：
Y. Kuroda;Michinori Ito;K. Toshima;E. Takeda;E. Naito;T. Hwang;T. Hashimoto;M. Miyao;M. Masuda;K. Yamashita;T. Adachi;Y. Suzuki;K. Nishiyama
对1例原因不明的乳酸中毒新生儿(例1)和1例合并乳酸中毒的15岁男童(例2)口服二氯乙酸钠(DCA)，剂量为每公斤体重50 mg，每日2~3次。例1在DCA治疗过程中，DCA在血液中蓄积，尿中DCA排泄量逐渐增加，血乳酸水平迅速降至正常范围。患者2在治疗过程中血中DCA水平逐渐升高，浓度为2 5 0µg/L−1，血乳酸水平下降并维持在正常范围内。患者1尸检时脑组织(2 5µg组织−1)、肝、肾和肌肉(分别为33.8、33.8和2 6.3µg组织−1)和患者2的脑脊液中检测到DCA，当−1血药浓度为2 5 0µg ml时，脑脊液中乳酸水平分别从7和4 mmoll−1降至2.4和2.6mmoll−1。因此，DCA可能在临床治疗慢性先天性乳酸酸中毒有用，因为它似乎跨越了血脑屏障。然而，它必须以无毒剂量给药，通过监测血液中乳酸和DCA的浓度来确定，因为口服DCA往往会在组织中积累。
Sodium dichloroacetate (DCA) was administered orally at a dose of 50 mg per kg body weight twice or three times per day to a newborn infant with lactic acidosis of unknown cause (patient 1) and to a 15-year-old boy with mitochondrial encephalomyopathy associated with lactic acidosis (patient 2). In patient 1, during treatment with DCA, DCA accumulated in the blood judging from the findings that the urinary excretion of DCA increased cumulatively and the blood lactate level rapidly decreased to the normal range. In patient 2, the blood DCA level gradually increased during treatment to a concentration of 250 µgml−1 and the blood lactate level decreased and was maintained within the normal range. DCA was detected in the brain (25 µg g tissue−1) and the liver, kidney and muscle (33.8, 33.8 and 26.3 µg g tissue−1, respectively) obtained at autopsy of patient 1, and in the cerebrospinal fluid of patient 2 at a concentration of 125 µg ml−1 when the blood concentration was 250 µg ml−1. The lactate levels in the cerebrospinal fluid decreased from 7 and 4mmoll−1 to 2.4 and 2.6 mmoll−1 in patients 1 and 2, respectively. Thus DCA may be useful in clinical treatment of chronic congenital lactic acidosis because it seems to cross the blood-brain barrier. However, it must be given at non-toxic doses, determined by monitoring the concentrations of lactate and DCA in the blood, because orally administered DCA tends to accumulate in tissues.
影响因子：
5.8
作者：
EVANS, OB;STACPOOLE, PW
通讯作者：
STACPOOLE, PW