EFFECTS OF CONCURRENT ADMINISTRATION OF FLOSEQUINAN AND DIGOXIN ON THE PHARMACOKINETICS OF EACH DRUG

The pharmacokinetic and pharmacodynamic effects of co-administration o f flosequinan (BTS 49465, CAS 76568-02-0) and digoxin (CAS 20830-75-5) were investigated in 12 healthy volunteers. A 4-day, open, lead-in ph ase established the pharmacokinetics of flosequinan (100 mg on the fir st day and 50 mg for the next 3 days) and was followed by a 24-day ope n interaction phase. Digoxin was administered alone (0.75 mg for the f irst 3 days and 0.5 mg for the next 4 days) to establish steady-state pharmacokinetics and in combination with flosequinan (100 mg on the 8t h day and 50 mg for the next 14 days with 0.5 mg digoxin daily), and f inally digoxin alone (0.5 mg for the remaining 3 days). No statistical ly significant differences were observed for any of the pharmacokineti c parameters for flosequinan, its major metabolite BTS 53554, or dioxi n when flosequinan and digoxin were administered alone or concomitantl y, but the confidence intervals for differences were relatively wide. Overall diastolic blood pressure was significantly lowered hy 10 % wit h concomitant treatment compared with flosequinan monotherapy. There w ere no significant effects on overall heart rate or systolic blood pre ssure, although pre-dose heart rate was increased by 6 % during concom itant administration compared with digoxin alone, and remained high an d digoxin alone. Adverse events (headache, nausea and vomiting) were r eported by 2 volunteers on digoxin and 5 on concomitant therapy. One v olunteer was withdrawn during concomitant therapy because of severe he adache and vomiting The results from this study indicate that no pharm acokinetic interaction occurred during concomitant administration of f losequinan and digoxin in healthy volunteers.