Influence of carvedilol on serum digoxin levels in heart failure: is there any gender difference?
The activity of the human cytochrome P450 and P-glycoprotein (P-gp) changes according to gender. The present study evaluated the effect of gender on the influence of carvedilol on serum digoxin levels in patients with heart failure. Twenty-four patients (12 female and 12 male) with New York Heart Association class II-III heart failure were included in the study. Patients were taking oral digoxin (0.0625–0.25 mg, once a day) and were administered oral carvedilol (6.25 mg, two times daily) for 7 days. In the male group, carvedilol led to statistically significant increases in the area under the concentration time curve to 16 h (AUC0–16h) and the peak concentration (Cmax) for digoxin, with no change in time to peak (tmax)(AUC0–16h= 24.1±9.2 ng.h/ml vs. 15.4±5.8 ng.h/ml, p<0.001, Cmax=2.2±1.0 ng/ml vs. 1.6±0.6 ng/ml, p<0.01, tmax=2.4±2.2 h vs. 2.1±1.0 h, p>0.05). In the female group, carvedilol administration did not cause statistically significant change in the AUC0–16h, Cmax, or tmax for digoxin (p>0.05). In the male group, carvedilol resulted in a significant increase in the AUC0–16h and Cmax for digoxin compared with the female group (AUC0–16h=24.1± 9.2ng.h/ml vs. 17.0±6.8 ng.h/ml, Cmax=2.2±1.0 ng/ml vs. 1.5±0.6 ng/ml, p<0.05, respectively). Men seem to have a higher activity relative to women for the drug efflux transporter P-gp. Our results suggest that carvedilol will cause drug interaction with digoxin following the inhibition of P-gp-mediated transcellular transport of digoxin in males.