Zannad F, Marchal F, Royer R J, Vert P, Robert J
Pediatr Pharmacol (New York). 1981;1(3):221-9.
In general, there is little agreement how digoxin should be used in newborn, and the results of studies in this field seem contradictory. This study attempts a quantitative assessment of the number and the sensitivity of cellular receptors for digoxin in the organism, by the in vitro measurement of erythrocyte 86Rubidium uptake in neonates compared with adults and old people. Red blood cells are first incubated with differing concentrations of digoxin, and then incubated with 86Rb. The initial level of 86Rb uptake (Rbi) is that observed in the absence of digoxin. The 50% index of captation (IC50) is the digoxin concentration in nanograms per ml at which 86Rb uptake is half Rbi. Three groups of patients were studied: Group I: 12 neonates, less than 5 days old; Group II: 11 adults (26 to 57 years old); Group III: 9 elderly people (71 to 82 years old). Rbi was significantly lower in neonates (Mean +/- SD: 25.8% +/- 3.5, P less than 0.001) and in the elderly (29.9% +/- 3.1) than in adults (36.8% +/- 4.6). IC50 was significantly lower in the elderly (12.1 ng/ml +/- 2.4) than in the adult patients (20.5 ng/ml +/- 5.5, P less than 0.001). In the newborns, values of IC50 were widely scattered (16.2 ng/ml +/- 7.2). The authors suggest that since Rbi reflects Na+, K+-ATPase activity, this activity is diminished in newborn and old people, and indicates that they have fewer cellular receptors for digoxin than adults. In the elderly, the low IC50 would imply increased sensitivity to digoxin. In neonates, the wide range of values for IC50 suggests considerable individual variation in sensitivity to digoxin. The results are consistent with the recently recommended lower dosages of digoxin in neonates.
一般来说,关于地高辛在新生儿中的使用方法几乎没有一致的意见,该领域的研究结果似乎相互矛盾。本研究试图通过体外测量新生儿与成年人及老年人红细胞对86铷的摄取量,对机体中地高辛细胞受体的数量和敏感性进行定量评估。红细胞首先与不同浓度的地高辛孵育,然后与86铷孵育。86铷摄取的初始水平(Rbi)是在无地高辛情况下观察到的水平。50%摄取指数(IC50)是使86铷摄取量为Rbi一半时每毫升纳克的地高辛浓度。研究了三组患者:第一组:12名出生不到5天的新生儿;第二组:11名成年人(26至57岁);第三组:9名老年人(71至82岁)。新生儿(平均值±标准差:25.8%±3.5,P<0.001)和老年人(29.9%±3.1)的Rbi显著低于成年人(36.8%±4.6)。老年人的IC50(12.1纳克/毫升±2.4)显著低于成年患者(20.5纳克/毫升±5.5,P<0.001)。在新生儿中,IC50值分布广泛(16.2纳克/毫升±7.2)。作者认为,由于Rbi反映钠钾ATP酶活性,该活性在新生儿和老年人中降低,表明他们的地高辛细胞受体比成年人少。在老年人中,低IC50意味着对地高辛的敏感性增加。在新生儿中,则意味着对地高辛的敏感性个体差异很大。这些结果与最近推荐的新生儿较低地高辛剂量一致。