HYPOKALEMIA IN HEALTHY-VOLUNTEERS AFTER SINGLE AND MULTIPLE DOSES OF FORMOTEROL OR SALBUTAMOL

A specific beta(2)-adrenoceptor-mediated effect, hypokalaemia, was stu died in healthy volunteers after single as well as multiple dosages of the long-acting agonist formoterol and the short-acting agent salbuta mol. The purpose of the study was to test with simple methodologies if rapidly induced tachyphylaxis for this well known systemic effect can be shown and if it will then be more pronounced for the long-acting c ompound. Hypokalaemia induced by inhalation of, respectively, 72 mu g formoterol and 1200 mu g of salbutamol was studied before and after 1 week of medication. Potassium-time curves were described by a biexpone ntial equation and also analysed with a deconvolution technique. Both drugs induced a statistically significant hypokalaemia. the duration o f this effect bring considerably shorter for salbutamol than for formo terol (p < 0.05 with both methods of analysis). After multiple doses f or 1 week, both maximal hypokalaemia and the area under the curve of t he hypokalaemic effect had decreased after inhalation of formoterol (p < 0.05) but not after inhalation of salbutamol. It was concluded that plasma potassium as an effect measurement can be used to study in a s imple but reproducible way differences of pharmacological interest bet ween various beta(2)-adrenoceptor agonists.