Button C, Gross D R, Johnston J T, Yakatan G J
Am J Vet Res. 1980 Aug;41(8):1230-7.
Digoxin, 30 micrograms/kg, was given by IV injection and orally, in the forms of pediatric elixir and tablet, on three separate occasions to six healthy dogs. Multiple serum samples were collected at timed intervals and assayed by radioimmunoassay. Data were analyzed, using nonlinear least squares regression analysis. The mean serum digoxin-time relationship was triexponential. Rapid and slow distributive phases with half lives of 9 minutes and 4.7 hours were followed by a biological disposition phase with a half life of 30.1 hours. Mean volume of distribution by extrapolation was 15.6 L/kg. When calculated by the area method, mean volume of distribution was 12.4 L/kg. Digoxin elixir was rapidly absorbed, with a mean bioavailability estimate of 71.4 +/- 8.2% SD. Digoxin tablets were less rapidly and less completely absorbed, with a mean bioavailability estimate of 58.0 +/- 11.6%. Data collected in this series of experiments and data from the literature were applied to standard pharmacokinetic equations to formulate loading and maintenance doses of digoxin for the IV injection, the elixir, and the tablet. Mean loading doses were, in micrograms/kg/24 hours: 27, 38, and 45 for the IV injection, elixir, and tablet, respectively. Corresponding mean maintenance doses were 13, 18, and 23.
以静脉注射、小儿酏剂和片剂的形式,在三个不同的时间点给6只健康犬分别给予地高辛,剂量为30微克/千克。按预定时间间隔采集多个血清样本,并用放射免疫分析法进行测定。采用非线性最小二乘回归分析法对数据进行分析。血清地高辛-时间关系呈三指数型。分布的快速相和缓慢相半衰期分别为9分钟和4.7小时,随后是生物处置相,半衰期为30.1小时。外推法得出的平均分布容积为15.6升/千克。用面积法计算时,平均分布容积为12.4升/千克。地高辛酏剂吸收迅速,平均生物利用度估计值为71.4±8.2%标准差。地高辛片剂吸收较慢且不完全,平均生物利用度估计值为58.0±11.6%。将这一系列实验收集的数据以及文献数据应用于标准药代动力学方程,以制定静脉注射、酏剂和片剂的地高辛负荷剂量和维持剂量。平均负荷剂量(微克/千克/24小时)分别为:静脉注射27、酏剂38、片剂45。相应的平均维持剂量分别为13、18和23。