TOLERABILITY TO HIGH-DOSES OF FORMOTEROL AND TERBUTALINE VIA TURBUHALER(R) FOR 3 DAYS IN STABLE ASTHMATIC-PATIENTS

This randomized, double-blind, crossover study in two parts compared t olerability to high doses of formoterol (Oxis(R) Turbuhaler(R)) with t hat of high doses of terbutaline (Bricanyl(R) Turbuhaler(R)). After Ho lter monitoring at home, 12 patients were treated with 4+4+4 doses of formoterol Turbuhaler, 6 mu g.dose(-1), (total daily metered dose 72 m u g) or 4+4+4 doses of terbutaline Turbuhaler, 0.5 mg.dose(-1) (daily dose 6 mg) given in the morning, after lunch and in the evening, for 3 consecutive days. After a one week washout period at home, patients r eceived the alternative treatment. Thereafter, 15 other patients recei ved 8+6+6 doses of formoterol Turbuhaler (total daily metered dose 120 mu g) or potassium 8+6+6 doses of terbutaline Turbuhaler (daily dose 10 mg). Pulse, cardiac frequency, blood pressure, serum potassium, ele ctrocardiogram and forced expiratory volume in one second (FEV1) were registered at regular intervals and Holter monitoring was applied duri ng all 4 treatment days. Terbutaline 6 mg showed significantly greater systemic effects than formoterol 72 mu g on pulse, blood pressure, ca rdiac frequency and QTc (QT interval corrected for heart rate). Terbut aline 10 mg had significantly greater effects than formoterol 120 mu g on serum potassium levels, pulse, cardiac frequency and QTc. No diffe rences in FEV1 levels mere found. Both drugs were safe and generally w ell tolerated on both dose levels. In conclusion, high doses of formot erol Turbuhaler over 3 days were generally safe and well tolerated. Da ily doses of 6 mg and 10 mg terbutaline Turbuhaler were systemically m ore potent than 72 mu g and 120 mu g formoterol, respectively. The saf ety margin thus appears to be wide if patients happen to use extra dos es of formoterol in addition to those prescribed for regular use.