The pharmacokinetics of the enantiomers of atenolol

A number of studies have demonstrated that lipophilic β-adrenoceptor blocking agents, eliminated almost exclusively by hepatic metabolism, are stereoselectively metabolized in human beings. Previous studies in our laboratory have demonstrated that pindolol, a β-adrenoceptor blocking agent of intermediate lipophilicity that is eliminated by both hepatic metabolism and renal excretion, is eliminated stereoselectively in the kidney. In the present study we examined the pharmacokinetics of the enantiomers of atenolol, a hydrophilic cardioselective β-adrenoceptor blocking agent that is eliminated almost exclusively by the kidney. A single 100 mg oral dose of racemic atenolol was administered to six healthy adult men. Concentrations of d- and l-atenolol in plasma and urine were measured by a stereospecific HPLC analytic procedure. In each subject the peak concentration of l-atenolol was greater than the peak concentration of l-atenolol (mean ± SD of 420 ± 81 ng/ml vs 366 ± 61 ng/ml; p < 0.05). The peak concentration of both enantiomers was reached at the same time in each subject (between 2 and 3 hours). The renal clearances of d- and l-atenolol were not significantly different (109.7 ± 33.5 ml/min vs 112.5 ± 36.7 ml/min), probably because the major route of renal elimination is glomerular nitration. The half-lives of d and l-atenolol were not significantly different (mean ± SD of 4.6 ± 1.1 hours vs 5.2 ± 0.9 hours). However, both the AUC and the amount excreted unchanged in the urine in 24 hours Ae [0–24]) were significantly greater for d-atenolol than for l-atenolol (p < 0.05). These data suggest that the bioavailability of atenolol is stereoselective. Although the magnitude of the stereoselectivity was small and the ratio of the active to inactive enantiomer did not differ greatly from unity, the mechanism responsible for the stereoselectivity is of interest in light of the very low metabolic clearance of atenolol. A possible mechanism that may account for the stereoselective bioavailability is stereoselective active absorption. Clinical Pharmacology and Therapeutics (1989) 45, 403–410; doi:10.1038/clpt.1989.47