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Bioavailability in man of atenolol and chlorthalidone from a combination formulation
Author(s) -
McAinsh James,
Holmes Brian H.,
Fitzsimons Timothy J.,
Young Jean
Publication year - 1986
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510070303
Subject(s) - atenolol , chlorthalidone , bioavailability , pharmacology , area under the curve , urinary system , pharmacokinetics , chemistry , medicine , diuretic , blood pressure
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 drugs as a fixed combination (‘Tenoret 50’), as a free combination, and individually, at doses of 50 mg atenolol and 12.5 mg chlorthalidone. There were no statistically or clinically significant differences between the three treatments of atenolol in terms of individual blood levels, areas under the curve, and urinary excretion. The mean half‐lives were between 5 and 7h, in agreement with other published data. The variation in peak systemic levels is less than that observed for a number of other β‐blocking drugs and is of the same order as seen in other investigations involving atenolol. Thus the bioavailability of atenolol from the fixed combination is equivalent to that from the free combination and from the atenolol tablet. The mean peak blood concentrations of chlorthalidone were 0.94, 1.00, and 0.99 μg ml −1 for the fixed and free combinations and the chlorthalidone tablet, respectively. The mean areas under the curve were also similar as were the mean half‐lives and urinary recovery. There were no statistically or clinically significant differences between the three treatments. Thus the bioavailability of chlorthalidone from the fixed combination is equivalent to that from the free combination and from the chlorthalidone tablet. It is concluded that combining chlorthalidone and atenolol in a single tablet does not affect the systemic bioavailability of either component.