Keller F, Blumenthal H P, Maertin K, Rietbrock N
Eur J Clin Pharmacol. 1977 Dec 16;12(5):387-92. doi: 10.1007/BF00562456.
Five healthy volunteers received digoxin 0.4 mg or beta-methyldigoxin 0.4 mg i.v., daily for 14 days, in a randomized cross-over arrangement. By monitoring minimal plasma concentrations during multiple dosing, it was found that the steady state pharmacokinetics of digoxin and beta-methyldigoxin could be estimated even better by a one-compartment than by a two-compartment model. The following mean parameters were calculated: the half life of digoxin of 1.54 +/- 0.31 days was significantly shorter than the half life of 2.29 +/- 0.34 days for beta-methyldigoxin. The distribution volume of 807 +/- 187 liters for digoxin was not significantly larger than the 735 +/- 227 liters for beta-methyldigoxin. Renal digoxin clearance of 191 +/- 25 ml/min was significantly higher than both the renal clearance of beta-methyldigoxin of 111 +/- 23 ml/min and also the creatinine clearance, which indicates tubular secretion of digoxin. There was a 2.8-fold accumulation of beta-methyldigoxin injected once a day, which was significantly higher than the 1.80-fold accumulation of digoxin.
五名健康志愿者按随机交叉安排，静脉注射地高辛0.4毫克或β-甲基地高辛0.4毫克，每日一次，共14天。通过监测多次给药期间的最低血浆浓度，发现与二室模型相比，一室模型能更好地估算地高辛和β-甲基地高辛的稳态药代动力学。计算出以下平均参数：地高辛的半衰期为1.54±0.31天，明显短于β-甲基地高辛的半衰期2.29±0.34天。地高辛的分布容积为807±187升，并不显著大于β-甲基地高辛的735±227升。地高辛的肾清除率为191±25毫升/分钟，显著高于β-甲基地高辛的肾清除率111±23毫升/分钟以及肌酐清除率，这表明地高辛存在肾小管分泌。每天注射一次的β-甲基地高辛有2.8倍的蓄积，显著高于地高辛的1.80倍蓄积。
