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地高辛在婴儿中的临床药代动力学。

Clinical pharmacokinetics of digoxin in infants.

作者信息

Wettrell G, Andersson K E

出版信息

Clin Pharmacokinet. 1977 Jan-Feb;2(1):17-31. doi: 10.2165/00003088-197702010-00002.

Abstract

Based on clinical experience, infants with congestive heart failure are given larger doses of digoxin than adults, whether calculated on the basis of body weight or surface area. The reasons for this difference in dosage are not clear. The myocardium of the infants might be more resistant to the effects of digoxin than that of adults, and/or differences might exist between infants and adults concerning the absorption, distribution and elimination of the glycoside. Infants have been found to absorb digoxin in solution at the same rate and to the same extent as adults. The relative distribution of the glycoside to different tissues is also similar in the two age-groups. However, the binding of digoxin to several tissues seems to be more extensive in infants than in adults. In agreement with this, the apparent volume of distribution of the glycoside is larger in infants than in adults. As no enhanced urinary excretion has been found in infants there might be a non-renal elimination of the glycoside. With most prevailing dose schedules for digoxin, serum concentrations higher than those considered optimum for adults are often obtained in infants. It is known that infants tolerate higher serum digoxin concentrations than adults without developing signs of toxicity. However, it is not known whether such high concentrations are necessary for obtaining an adequate inotropic effect on the myocardium of the infants. If the relation between serum concentration and effect is the same in infants and adults, the loading (digitalising) dose generally given to infants is unnecessarily high.

摘要

根据临床经验,无论以体重还是体表面积计算,患有充血性心力衰竭的婴儿所使用的地高辛剂量都比成人高。这种剂量差异的原因尚不清楚。婴儿的心肌可能比成人的心肌对地高辛的作用更具耐受性,和/或婴儿与成人在糖苷的吸收、分布和消除方面可能存在差异。已发现婴儿吸收溶液中的地高辛的速率和程度与成人相同。糖苷在不同组织中的相对分布在两个年龄组中也相似。然而,地高辛与几种组织的结合在婴儿中似乎比在成人中更广泛。与此一致的是,糖苷在婴儿中的表观分布容积比成人中的大。由于在婴儿中未发现尿排泄增加,可能存在糖苷的非肾消除。按照大多数常用的地高辛给药方案,婴儿的血清浓度常常高于认为对成人最佳的浓度。已知婴儿能耐受比成人更高的血清地高辛浓度而不出现毒性迹象。然而,尚不清楚如此高的浓度对于在婴儿心肌上获得足够的正性肌力作用是否必要。如果婴儿和成人中血清浓度与效应之间的关系相同,通常给予婴儿的负荷(洋地黄化)剂量就过高了。

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