Influence of Carbimazole on Serum Levels and Haemodynamic Effects of Digoxin

Although the influence of thyroid dysfunction on the effectiveness and disposition of drugs has been extensively studied, the pharmacokinetic/pharmacodynamic interactions between cardiac glycosides and antithyroid drugs have not been investigated. This possibility arose following the clinical observation of relatively lower digoxin plasma levels in 1 patient concomitantly treated with Carbimazole. We therefore examined the influence of a single oral dose of 60mg Carbimazole or placebo on the steady-state serum levels and haemodynamic effects of digoxin (0.375mg maintenance dose) in 10 healthy subjects according to a double-blind randomised crossover design. Serum digoxin levels were measured by the fluorescence polarisation immunoassay technique; haemodynamic parameters, cardiac output and stroke volume were determined by Doppler echo-aortography. Peak serum levels (Cmax) of digoxin were significantly lowered (1.72 ± 0.33 vs 1.33 ± 0.29 µtg/L, p = 0.0275) in 9 out of 10 subjects when digoxin was combined with Carbimazole. The mean time to reach peak levels (tmax) and area under the serum concentration-time curve (AUC0-24) were not significantly affected. However, serum digoxin levels rose considerably in 1 subject upon administration of Carbimazole (Cmax 1.08 to 2.38 µg/L and AUC0-24 12.75 to 23.85 µg/L·h). Systolic blood pressure was significantly lowered (p < 0.05) for 3 hours with digoxin alone, but not when Carbimazole was added. Diastolic blood pressure was also significantly (p < 0.05) reduced up to 12 hours with digoxin, but for for 6 hours with combination treatment. Despite the fact that the investigated drugs are structurally and functionally unrelated, these results suggest the need to monitor digoxin plasma levels when concomitantly administering antithyroid drugs.