Metoprolol renal clearance

The stereoselectivity in the plasma concentrations of metoprolol is mostly related to the stereoselective metabolism and first-pass effect of the drug. A slight stereoselectivity in the renal clearance of the drug in favor of R( )-metoprolol (Table 3) virtually has no effect on the plasma stereoselectivity because of the negligible contribution of this pathway to the overall elimination of the drug. Whereas a preferential metabolism of ( )-metoprolol in extensive metabolizers of debrisoquine results in a (—) ( ) AUC ratio of 1.37 0.32 [40], the stereoselectivity is reversed [(—) ( ) AUC ratio of 0.90 0.06] in poor metabolizers of debrisoquine (Table 3). 

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). 

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