Digoxin concentrations in serum and cantharides blister fluid: correlations with cardiac response.
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.
Schäfer-Korting
M
M
Pharmakologisches Institut für Naturwissenschaftler der Universität, Frankfurt, F.R.G.
Belz
G G
GG
Brauer
J
J
Alken
R G
RG
Mutschler
E
E
D000328:Adult; D001768:Blister / Q000378:metabolism*; D004077:Digoxin / Q000493:pharmacokinetics* / Q000494:pharmacology; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008297:Male; D013599:Systole / Q000187:drug effects
D004077:Digoxin