Penbutolol and furosemide in a fixed-dose combination-bio-equivalence of two formulations

Abstract

Twelve healthy male volunteers participated in an open cross-over study designed to test whether two fixed-dose combination formulations of penbutolol (40 mg) and furosemide (20 mg), an ordinary and a film-coated tablet, are bio-equivalent. Penbutolol capsules (40 mg) and 20 mg furosemide tablets (Lasix; Hoechst) served as reference formulations. The maximum concentration of furosemide was significantly depressed in the case of fixed-dose combinations, reflecting a possible pharmacokinetic interaction between penbutolol and furosemide. However, the area under the concentration versus time curve for furosemide and its cumulative urinary excretion and diuretic effect were not influenced by penbutolol. On the basis of plasma concentration versus time data and urinary parameters, the two fixed-dose formulations are bio-equivalent.