Digoxin pharmacokinetics in patients with high serum digoxin concentrations.
Digitalis intoxication is a frequent iatrogenic effect in patients on treatment with digoxin. In the present study we evaluated the pharmacokinetic behaviour of digoxin and the factors responsible for intoxication by this drug in monitored patients exhibiting clinical signs of overdosing with serum levels > 2 ng/ml. A control group of patients was used as a reference whose population pharmacokinetic parameters obtained by a maximum likelihood method were: Vd = 542.92 +/- 274.53 (litre); Cl = 8.73 +/- 1.55 (litre/h) (mean +/- SD). Statistically significant differences (P < 0.001) were found between the mean Cl values in both groups of patients. The difference between the dose-level ratios established in both populations studied also proved to be significant (P < 0.001). Calculation of the optimum dose for each patient showed that the doses recommended in intoxicated patients should be three times lower than those used in the control population. A good correlation was found between the concentrations observed 24 h after administration and the mean concentrations observed at steady state predicted for both population groups. Multiple regression analysis showed that the variables with the greatest predictive value for clearance in intoxicated patients were age and renal function. The modifications observed in the pharmacokinetic behaviour and in the response to digoxin in this type of patient suggest systematic monitoring using pharmacokinetic and clinical criteria jointly.
Martín-Suárez
A
A
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University Hospital, University of Salamanca, Spain.
Lanao
J M
JM
Calvo
M V
MV
Martín
P
P
Domínguez-Gil
A
A
D000328:Adult; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics* / Q000506:poisoning; D062787:Drug Overdose; D006801:Humans; D007049:Iatrogenic Disease; D008875:Middle Aged; D012189:Retrospective Studies
D004077:Digoxin