Schäfer-Korting M, Belz G G, Brauer J, Alken R G, Mutschler E
Pharmakologisches Institut für Naturwissenschaftler der Universität, Frankfurt, F.R.G.
Clin Pharmacol Ther. 1987 Dec;42(6):613-20. doi: 10.1038/clpt.1987.208.
The relationship between the pharmacokinetics and dynamics of digoxin was investigated using a skin blistering technique that allows experimental access to tissue fluid concentrations. Eight healthy volunteers received digoxin, 1.0 mg, and placebo intravenously according to a double-blind crossover design. Drug concentrations were determined during a 72-hour period in serum, urine, and cantharides blister fluid (CBF). Digoxin levels in the hypothetic peripheral compartments were calculated from serum concentrations. Digoxin effects (total electromechanical systole [QS2c], left ventricular ejection time [LVETc], preejection period [PEPc], QTc time, heart rate, and T wave amplitude) were measured simultaneously. Peak levels in the shallow and deep compartments occurred at 12 1/2 to 20 minutes and 3 hours and the maximum concentration in CBF (2.75 +/- 0.48 ng/ml) occurred at 1 hour. Digoxin effects on QS2c, PEPc, and the ratio PEP/LVET were not related to serum concentrations but were closely related to CBF concentrations (r = 0.90). CBF concentrations were then within the range of serum digoxin concentrations usually associated with the treatment of heart failure. Thus, CBF allows experimental access to active drug concentrations after a single intravenous dose.
采用皮肤起疱技术研究了地高辛的药代动力学与药效学之间的关系，该技术可使实验测得组织液浓度。8名健康志愿者按照双盲交叉设计静脉注射1.0毫克地高辛和安慰剂。在72小时内测定血清、尿液和斑蝥水疱液（CBF）中的药物浓度。根据血清浓度计算假设的外周隔室中的地高辛水平。同时测量地高辛效应（总电机械收缩期[QS2c]、左心室射血时间[LVETc]、射血前期[PEPc]、QTc时间、心率和T波振幅）。浅隔室和深隔室的峰值水平分别出现在12.5至20分钟和3小时，CBF中的最大浓度（2.75±0.48纳克/毫升）出现在1小时。地高辛对QS2c、PEPc和PEP/LVET比值的影响与血清浓度无关，但与CBF浓度密切相关（r = 0.90）。此时CBF浓度处于通常与心力衰竭治疗相关的血清地高辛浓度范围内。因此，单次静脉给药后，CBF可测得活性药物浓度。
