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 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 7 h, in agreement with other published data. The variation in peak systemic levels is less than that observed for a number of other beta-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 micrograms 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.

Prodrugs for Masking the Bitter Taste of Drugs

“…Atenolol has a pKa of 9.6; it undergoes ionization in the stomach and intestine thus its oral bioavailability is low due to inefficient absorption through membranes. The bioavailability of atenolol is 45%-55% of the given dose and is not increased by administration of the drug in a solution form [123][124][125].About 50% of administered atenolol is absorbed; however, most of the absorbed quantity reaches the systemic circulation. Atenolol peak blood levels are reached within two to four hours after ingestion.…”

Fixed‐Dosed Combinations Are Not Indicated as Initial Therapy: A Debate

“…The chlorthalidone blood levels were 10% higher and urinary excretion 24% higher following the administration of the FDC when compared with the free combination or the chlorthalidone tablet. 17 These studies suggest that pharmacokinetics and probably pharmacodynamics may differ with FDCs when compared with individual tablets. These types of studies are always conducted in young, healthy normal volunteers, with very little information in the elderly.…”

An observational comparative study of different doses of azilsartan and with chlorthalidone combination in moderate hypertension

“…Serum concentrations of chlorthalidone reaches its peak at approximately 2-6 hours. 7,8 The recommended starting dose of azilsartan/chlorthalidone is 40/12.5mg taken orally once daily. Most of the antihypertensive effect is apparent within 1 to 2weeks.…”