Bioavailability in man of atenolol and chlorthalidone from a combination formulation

Abstract

In this comparative bioavailability study in 12 healthy volunteers the blood level profiles and urinary recoveries of both atenolol and chlorthalidone were studied following the administration of the drug as a fixed combination (‘Tenoretic’), as a free combination, and individually, at doses of 100 mg atenolol, and 25 mg chlorthalidone.There were no statistically significant differences between the three formulations of atenolol in terms of individual blood levels, half‐life, area‐under‐the‐curve, and urinary excretion. The half‐lives were between 5 and 6 h in agreement with other published data. Thus the bioavailability of atenolol from the fixed combination is equivalent to that from the free combination and from the atenolol tablet.The chlorthalidone blood levels were slightly higher following the administration of the fixed combination when compared with the free combination or the chlorthalidone tablet. This observation was reflected in estimates of the area under the curves and the urinary recoveries. The half‐lives of all three formulations were similar at about 60 h.It is concluded that combining chlorthalidone and atenolol in a single tablet does not reduce the systemic bioavailability of either component.