Interaction of atenolol with furosemide and calcium and aluminum salts

Six healthy subjects were treated with 100 mg atenolol. After a therapy-free interval of 4 wk the same subjects received the same dose of atenolol with furosemide, 40 mg, with calcium (as the lactate gluconate and carbonate), 500 mg, or with aluminum hydroxide, 5.6 gm. Atenolol alone and in combination was administered first as a single oral dose; a long-term 6-day treatment began 48 hr later. Addition of furosemide did not influence atenolol kinetics, but aluminum hydroxide led to an insignificant reduction (P greater than 0.05) of mean peak plasma levels of about 20% and of the area under the plasma concentration-time curve (AUC -infinity) from 5818 to 4353 ng ml-1 hr (P greater than 0.05). Calcium altered atenolol kinetics distinctly mean peak plasma levels of atenolol fell 51% (P less than 0.001), AUC0-infinity fell from 5818 to 3935 ng ml-1 hr (P less than 0.01) and elimination half-life (t1/2) increased to a mean of 11.0 hr (compared to 6.2 hr with atenolol alone). The prolongation of t1/2 induced by calcium coadministration led to atenolol cumulation during the long-term dosage. Twelve hours after atenolol, 100 mg, and calcium, 500 mg, exercise tachycardia was lower than with atenolol alone (P less than 0.001). During the 4-wk treatment in six hypertensive patients, blood pressure values of those on atenolol alone were not different from those on the combination therapies (P greater than 0.05).