Summary
A study was made of the influence of hydralazine on the oral availability of atenolol, a low clearance hydrophilic β- adrenoceptor antagonist. Atenolol (100mg) was given orally alone or in combination with oral hydralazine (25 or 50mg) on separate occasions to 6 normal healthy volunteers. Blood samples were collected post- dose over 9 hours and urine samples for 24 hours. Assays for atenolol were performed using a specific high pressure liquid chromatography technique.
Peak concentrations of atenolol, time to peak and area under the plasma concentration- time curve (AUC) were not altered by coadministration of either dose of hydralazine. Similarly, there were no differences in the urinary recovery or renal clearance of atenolol.
These results are in agreement with findings on coadministration of hydralazine with other β- blockers (nadolol, acebutolol) with low hepatic clearance, but contrast with the findings of increased AUC and peak concentrations when hydralazine was coadministered with propranolol and metoprolol.
Combination therapy with β- blockers and vasodilators is widely used, exploiting pharmacodynamic synergism. If vasodilator- induced changes in splanchnic blood flow mediate alterations in oral availability, then all high clearance β- blockers may show this interaction, indicating potential therapeutic advantage for those β- blockers which show low hepatic clearance.
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McLean, A.J., Wilhelm, D. & Heinzow, B.G. Stable Oral Availability of Atenolol Coadministered with Hydralazine. Drugs 25 (Suppl 2), 131–135 (1983). https://doi.org/10.2165/00003495-198300252-00038
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DOI: https://doi.org/10.2165/00003495-198300252-00038