Wettrell G
Eur J Clin Pharmacol. 1977;11(5):329-35. doi: 10.1007/BF00566529.
The distribution and elimination of intravenous digoxin were investigated in seven neonates and infants with heart failure. Serum digoxin concentrations during a 24 h period were determined by radioimmunoassay, using 125I as tracer. The serum values declined biexponentially after the injection and could be fitted to a two-compartment open model by non-linear least-squares regression. The calculated mean half-lives of the distribution (alpha) phase in neonates and infants were 37 and 28 min, respectively. The mean half-life of the elimination (beta) phase in neonates was 44 h, as compared to 19 h in infants. The mean volume of the central compartment and the mean volume of distribution at steady-state were calculated to be 1.3 and 9.91/kg, respectively; no significant differences between neonates and infants were found. The relation between these volumes indicates that digoxin is extensively distributed in tissues. The steady-state distribution volumes of digoxin in neonates and infants exceed those reported in adults. The larger volume of distribution might explain in part why infants with cardiac insufficiency require larger doses of digoxin than adults (on a mg/kg body weight basis) to obtain the same serum concentrations. Elimination of digoxin from the body was slower in neonates than in infants.
对7例心力衰竭的新生儿和婴儿进行了静脉注射地高辛的分布和消除情况研究。以125I为示踪剂,采用放射免疫分析法测定24小时内的血清地高辛浓度。注射后血清值呈双指数下降,通过非线性最小二乘法回归可拟合为二室开放模型。计算得出新生儿和婴儿分布(α)相的平均半衰期分别为37分钟和28分钟。新生儿消除(β)相的平均半衰期为44小时,而婴儿为19小时。中央室平均容积和稳态分布容积经计算分别为1.3和9.91/kg;新生儿和婴儿之间未发现显著差异。这些容积之间的关系表明地高辛在组织中广泛分布。地高辛在新生儿和婴儿中的稳态分布容积超过了成人报告的数值。分布容积较大可能部分解释了为什么心脏功能不全的婴儿(以mg/kg体重计)比成人需要更大剂量的地高辛才能获得相同的血清浓度。地高辛从体内的消除在新生儿中比在婴儿中更慢。