Digoxin disposition in obesity: Clinical pharmacokinetic investigation

Olgoxin pharmacokinetics were studied in 16 obese (mean ± SD weight, 100.2 ± 36.8 kg) and 13 control (64.6 ± 10.5 kg) subjects. all subjects had normal renal function and no other coexisting disease. After administration of 0.75 mg digoxin by intravenous intusion, multiple plasma samples obtained over the 96 hours following infusion were analyzed for digoxin concentration by radloimmunoassay. Pharmacokinetic parameters were determined by weighted iterative nonlinear least squares regression analysis. Elimination half-life (t 1 2) was not different between obese and control groups (35.6 ± 10.5 vs 41.2 ± 16.7 hours). Absolute volume of distribution (Vd) also was not different (981 ± 301 vs 937 ± 397 liters), nor was total clearance of digoxin (328 ± 82 vs 278 ± 87 ml/min). Elimination t 1 2 was significantly negatively correlated with clearance among all subjects (r = -0.46; p < 0.01). Using percent ideal body weight (IBW) as a measure of obesity, no correlation was found between percent IBW and Vd (r = 0.03). Thus digoxin is simllarly distributed into IBW in obese and normal weight subjects, and there is no significant distribution of digoxin into excese body weight over IBW. In addition, there is no difference in total metabolic clearance or elimination half-life between obese and control subjects. Digoxin loading and maintenance dosage should be calculated on the basis of IBW, which reflects lean body mass, rather than TBW, which reflects adipose tissue weight in addition to lean body mass.