Long-term effect of almitrine bismesylate in patients with hypoxemic chronic obstructive pulmonary disease.

A long-term evaluation of the therapeutic efficacy and safety of oral almitrine bismesylate (AB) (50 mg twice daily) was made on 25 patients with COPD and moderate hypoxemia residing at an altitude of 1,500 m in a double-blind placebo-controlled study. Thirteen patients receiving AB (baseline PaO2, 54.3 +/- 4.9 mm Hg; mean +/- SD) and 12 patients receiving placebo (baseline PaO2, 53.0 +/- 4.1 mmHg) were periodically followed by arterial blood gas and other pulmonary function studies and plasma levels of AB. Eight patients receiving AB and nine patients receiving placebo were followed for 1 yr; all patients were followed for at least 90 days. AB administration resulted in an increase in PaO2 to 62.2 +/- 9.3 mm Hg (p less than 0.01) on Day 28. The increase was maintained until Day 360 (63.8 +/- 4.6 mm Hg; p less than 0.01). The mean plasma concentration of AB on Day 28 was approximately one-half that on Day 90 when the plasma level reached a near maximum. AB was associated with weight loss (five of 13 patients receiving AB lost more than 10% of their baseline body weight) and peripheral paresthesias of the lower extremities (three patients), both occurring at the peak plasma levels of the drug. We conclude that AB causes a long-term improvement in arterial oxygenation in hypoxemic patients with COPD residing at an altitude of 1,500 m. Our data suggest that lower doses of AB might produce the same effect on PaO2 with less adverse associated effects, and this should be tested in future studies.