Objective: 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.
Methods: 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.
Results: In the male group, carvedilol led to statistically significant increases in the area under the concentration time curve to 16 h (AUC(0-16h)) and the peak concentration (C(max)) for digoxin, with no change in time to peak (t(max))(AUC(0-16h)= 24.1+/-9.2 ng.h/ml vs. 15.4+/-5.8 ng.h/ml, p<0.001, C(max)=2.2+/-1.0 ng/ml vs. 1.6+/-0.6 ng/ml, p<0.01, t(max)=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 AUC(0-16h), C(max), or t(max) for digoxin (p>0.05). In the male group, carvedilol resulted in a significant increase in the AUC(0-16h) and C(max) for digoxin compared with the female group (AUC(0-16h)=24.1+/- 9.2ng.h/ml vs. 17.0+/-6.8 ng.h/ml, C(max)=2.2+/-1.0 ng/ml vs. 1.5+/-0.6 ng/ml, p<0.05, respectively).
Conclusion: 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.