INFLUENCE OF CARBIMAZOLE ON SERUM LEVELS AND HEMODYNAMIC-EFFECTS OF DIGOXIN

Although the influence of thyroid dysfunction on the effectiveness and disposition of drugs has been extensively studied, the pharmacokineti c/pharmacodynamic interactions between cardiac glycosides and antithyr oid drugs have not been investigated. This possibility arose following the clinical observation of relatively lower digoxin plasma levels in I patient concomitantly treated with carbimazole. We therefore examin ed 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 Dopple r echo-aortography. Peak serum levels (C-max) of digoxin were signific antly lowered( 1.72 +/- 0.33 vs 1.33 +/- 0.29 mu g/L, p = 0.0275) in o ut of 10 subjects when digoxin was combined with carbimazole. The mean time to reach peak levels (t(max)),, and area under the serum concent ration-time curve (AUC(0-24)) were not significantly affected. However , serum digoxin levels rose considerably in I subject upon administrat ion of carbimazole (C-max 1.08 to 2.38 mu g/L and AUC(0-24) 12.75 to 2 3.85 mu g/L.h). Systolic blood pressure was significantly lowered (p < 0.05) for 3 hours with digoxin alone, but not when carbimazole was ad ded. Diastolic blood pressure was also significantly (p < 0.05) reduce d up to 12 hours with digoxin, but for for 6 hours with combination tr eatment. 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 dr ugs.