title: Is the mode of action of almitrine bismesylate dose dependent?
abstract: In order to assess whether different doses and/or plasma levels of almitrine bismesylate (ABM) could induce preferential effects on ventilation or on lung perfusion, we performed a single-blind placebo-controlled study of ABM treatment with different dosages (0.75, 1.5 and 2.25 mg.kg-1 single oral dose) in 26 patients suffering from chronic obstructive pulmonary disease (COPD). All measurements were performed according to the same time table. At control and at three 1.5-hour intervals, we measured alveolar-arterial (A-a) differences, alveolar dead space, total ventilation and ABM plasma levels. The effect on ventilation was estimated using changes in ventilatory parameters and (A-a)O2 differences. The effect on perfusion was indirectly estimated by analysis of arterial-end-tidal (a-ET)CO2 difference and alveolar dead space. The response to treatment was significant for the 1.5- and the 2.25-mg.kg-1 ABM groups, but not for the 0.75 mg.kg-1 ABM and the placebo group. A ventilatory response was often present in both 1.5- and 2.25-mg.kg-1 ABM groups, but a nonventilatory effect was present only at the highest dose according to the Severinghaus and Stupfel concept. Only the parameters reflecting an effect of the distribution of perfusion (a-ET)CO2 difference and alveolar dead space were significantly correlated with ABM plasma levels. The results suggest that a dose-dependent effect of ABM on lung perfusion may explain the controversial data in the literature about the mode of action of ABM.
authors.affiliation: Service d'Exploration de la Fonction Respiratoire, Hôpital Aiguelongue, Montpellier, France.
authors.forename: C
authors.initials: C
authors.lastname: Le Merre
authors.forename: J C
authors.initials: JC
authors.lastname: Ansquer
authors.forename: M J
authors.initials: MJ
authors.lastname: Clark
authors.forename: N
authors.initials: N
authors.lastname: Zouari
authors.forename: C
authors.initials: C
authors.lastname: Préfaut
mesh_terms: D000284:Administration, Oral; D000368:Aged; D015765:Almitrine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000188:drug therapy*; D008297:Male; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011897:Random Allocation
chemical_list: D015765:Almitrine