Singh S, Gadgil S, Mirkin B L
Res Commun Chem Pathol Pharmacol. 1978 Jul;21(1):87-101.
H3-digoxin pharmacokinetics following intravenous pulse injections was studied in dogs ranging in age from 0.5--2 days (n=2), 3--10 days (n=6), 11--30 days (n=5), 31--90 days (n=3) and adult dogs (n=5). All animals in each age group exhibited a biexponential elimination of H3-digoxin from the vascular compartment and data are analyzed by use of a two compartment pharmacokinetic model. Pharmacokinetic parameters showed significant age related differences. The mean T1/2(alpha) was greater in puppies aged 0.5--2 (8.92 +/- 2.61 min), 3--10 (11.8 +/- 1.99 min) and 11--30 days (10.32 +/- 1.89 min) when compared to adult dogs (5.36 +/- 0.91 min). The mean T1/2(beta) was four times longer in 3--10 day old dogs (1342.05 min) than in adult dogs (327.0 min) and decreased with increasing age of the puppies. The beta-phase rate constants were statistically different (p less than 0.05) between 3--10 day old and adult dogs. Elimination of H3-digoxin was slower in puppies than adult dogs (Kel in 3--10 day old puppies = 0.0046 min(-1); adult dogs = 0.0197 min(-1)) and was accompanied by a lower clearance of H3-digoxin in 3--10 day old puppies (2.05 ml/min/kg) than in adult dogs (7.41 ml/min/kg) [p less than 0.0001]. Functional immaturity of the canine kidney during early development probably constitutes the physiologic basis for the differences noted in H3-digoxin kinetics. While these distinctions in elimination kinetics are age related they do not clarify why younger organisms tolerate higher digoxin levels than adults with less apparent toxicity.
在年龄范围为0.5 - 2天（n = 2）、3 - 10天（n = 6）、11 - 30天（n = 5）、31 - 90天（n = 3）的幼犬及成年犬（n = 5）中研究了静脉脉冲注射后H³ - 地高辛的药代动力学。每个年龄组的所有动物均表现出H³ - 地高辛从血管腔室的双指数消除，并且数据通过使用二室药代动力学模型进行分析。药代动力学参数显示出与年龄相关的显著差异。与成年犬（5.36 ± 0.91分钟）相比，0.5 - 2天（8.92 ± 2.61分钟）、3 - 10天（11.8 ± 1.99分钟）和11 - 30天（10.32 ± 1.89分钟）的幼犬的平均T1/2(α)更长。3 - 10日龄犬的平均T1/2(β)（1342.05分钟）是成年犬（327.0分钟）的四倍，并且随着幼犬年龄的增加而降低。3 - 10日龄犬与成年犬之间的β相速率常数在统计学上存在差异（p < 0.05）。幼犬中H³ - 地高辛的消除比成年犬慢（3 - 10日龄幼犬的Kel = 0.0046分钟⁻¹；成年犬 = 0.0197分钟⁻¹），并且3 - 10日龄幼犬中H³ - 地高辛的清除率（2.05毫升/分钟/千克）低于成年犬（7.41毫升/分钟/千克）[p < 0.0001]。犬早期发育过程中肾脏功能不成熟可能是H³ - 地高辛动力学差异的生理基础。虽然这些消除动力学差异与年龄相关，但它们并未阐明为何较年幼的生物体比较成年生物体能够耐受更高的地高辛水平且毒性不那么明显。
