LACK OF PHARMACODYNAMIC INTERACTIONS BETWEEN ACUTE DOSE FLOSEQUINAN AND XAMOTEROL - A PILOT-STUDY IN HEALTHY-SUBJECTS

The possible cardiovascular pharmacodynamic interactions at rest and d uring exercise of combining oral flosequinan (100 mg) with xamoterol ( 200 mg) was investigated in a four-way randomised double-blind placebo -controlled crossover trial in eight healthy male volunteers. Xamotero l was better tolerated than flosequinan. The most common adverse event s were mild to moderate headache and facial flushing. One volunteer de veloped headache and vomiting following flosequinan treatment and was replaced. Compared to placebo, at supine rest, flosequinan significant ly increased heart rate (HR) by 5 beats min-l, but had no effect on ca rdiac output (CO), stroke volume (SV) and mean blood pressure (MBP). X amoterol significantly increased CO by 1.5 l.min(-1), HR (5 beats min( -1)) and MBP (6 mmHg) but not SV. The com bined treatment (flosequinan + xamoterol) significantly increased CO (1.7 l.min(-1)) and HR (10 be ats min(-1)), but had no effect on SV and MBP. During exercise, floseq uinan had no significant effect on any variable compared to placebo. B oth xamoterol and combined treatment reduced the increase in CO (-4.61 min(-1) after xamoterol and -3.41 min(-1) after combined treatment vs . 0.1 l.min(-1) after placebo), but had no effect on other variables. The effect of the combined treatment on each haemodynamic variable wer e no more than the anticipated additive effects of the two drugs. Thus , no cardiovascular pharmacodynamic interaction was found between flos equinan and xamoterol in healthy