Atenolol renal clearance

As mentioned above, renal excretion of the unchanged drug is the primary elimination pathway for hydrophilic beta-blockers such as atenolol, nadolol, and sotalol. In contrast to metabolism, the reported stereoselectivity in the renal clearance of beta-blockers is relatively low, with (—) (-f)... 

The paucity of QSAR studies in whole animals is understandable in terms of the costs, the heterogeneity of the biological data, and the complexity of the results. Nevertheless, in the few studies that have been done, excellent QSAR have been obtained, despite the small number of subjects in the data set (164). One particular example is insightful. The renal and nonrenal clearance rates of a series of 11 jS-blockers, including bufuralol, tolamolol, propranolol, alprenolol, oxprenolol, acebutol, timolol, metoprolol, prindolol, atenolol, and nadolol were measured (230). The following QSAR were formulated using those data (164). 

Medications whose excretion is primarily renal and for which there is evidence of age-related reduction in renal and total body clearance include (but are not limited to) amantadine, aminoglycosides, atenolol, captopril, cimetidine, digoxin, lithium, and vancomycin. Some hepatically metabolized medications can yield active, primarily renally excreted metabolites such as iV-acetylprocainamide, normeperidine, and morphine-6-glucuronide, which can accumulate with advancing age owing to reduced renal function. 

Another physicochemical parameter with some clinical correlation is the relative lipophilicity of different agents. Propranolol is by far the most lipophilic of the available P-blockers, and it enters the CNS far better than the less lipophilic agents, such as atenolol or nadolol. Lipophilicity as measured by octanol-water partitioning also correlates with the primary site of clearance, as seen in Table 13.8. The more lipophilic drugs are primarily cleared by the liver, whereas the more hydrophilic agents are cleared by the kidney. This could influence the choice of agents in cases of renal failure or liver disease. Several of the p-blockers must be dose adjusted in patients with impaired renal function, as indicated in Table 13.7. 

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