Resumen de Influence of trazodone on digoxin pharmacokinetics

Emilio Monteagudo Santolaya, Ana Pelufo Pellicer, Álvaro Briz Redón, Agustín Sánchez Alcaraz, Miguel Murcia Soler, Mª J. Company Albir

• Objective: The pharmacokinetic characteristics of digoxin make monitoring of plasma concentrations essential to optimize the dose. The combination of digoxin and trazodone can result in elevated plasma levels of digoxin. The objective is to assess the possible influence of trazodone as an inhibitor of digoxin clearance.

  Method: Retrospective study that includes patients on concomitant treatment with digoxin and trazodone. The actual digoxin and subsequently the estimated clearances were calculated using the PKS® pharmacokinetic program and the HUGE-DIG nomogram. The ratios (R) of estimated clearance versus actual clearance were compared separately between clusters of patients determined using the k-means algorithm.

  Results: Of the 51 registered patients, finally 20 were included in the study. Statistically significant differences were found in both analyzes. In 14 of the 20 patients, the calculated clearance of digoxin was lower than the clearance estimated by the PKS® program, with a difference of log (R) between clusters of 0.8, a 95% CI (0.59-1.01) and a value of p = 4.7 × 10–7. In the second analysis, of the eight patients with clearance estimated by the HUGE-DIG nomogram available, in five of them the calculated clearance of digoxin was lower than that estimated by the HUGE-DIG nomogram, with a difference of log (R) between clusters of 0.83, a 95% CI (0.54-1.13) and a value of p = 4.7 × 10–4.

  Conclusions: There were significant differences between the actual clearance of digoxin and the clearances estimated by PKS® and the HUGE-DIG nomogram, suggesting an influence of trazodone on the plasma clearance of digoxin. Close monitoring of digoxin plasma levels is necessary to make an adequate dosage adjustment and to carry out more studies to confirm these results