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DRUG METABOLISM

Influence of Chronic Renal Failure on Stereoselective Metoprolol Metabolism in Hypertensive Patients

Paula Macedo Cerqueira, Eduardo Barbosa Coelho, Tufik José Magalhães Geleilete, Gustavo Henrique Goldman and Vera Lucia Lanchote

From Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo-SP, Brazil (P. M. Cerqueira); Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto-SP, Brazil (E. B. Coelho, T. J. M. Geleilete); and Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto-SP, Brazil (G. H. Goldman, V. L. Lanchote).

The influence of chronic renal failure on the stereoselective metabolism of rac-metoprolol was investigated in 15 hypertensive patients, 7 of them with chronic renal failure and 8 with normal renal function. They were treated with rac-metoprolol (200 mg) for 7 days. The patients of both groups presented stereoselectivity in metoprolol metabolism, favoring the formation of 1'R-{alpha}-hydroxymetoprolol () and (R)-metoprolol acidic metabolite (), the latter resulting in the plasma accumulation of (S)-metoprolol (). Patients with chronic renal failure presented plasma accumulation of the 4 {alpha}-hydroxymetoprolol isomers and of both metoprolol acidic metabolite enantiomers. A 50% reduction in ClR does not explain the 3- to 4-fold plasma accumulation of metoprolol acidic metabolite in this group, suggesting that other pathways of metoprolol elimination are affected in chronic renal failure in addition to renal excretion. Chronic renal failure does not change the stereoselective kinetic disposition of metoprolol but modifies its stereoselective metabolism, inducing some of the CYP enzymes involved in the formation of the metoprolol acid metabolite.

Key Words: Metoprolol • stereoselectivity • metabolism • pharmacokinetics • chronic renal failure

Address for reprints: Vera Lucia Lanchote, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Avenida do Café s/n. Campus da USP, 14040-903, Ribeirão Preto, SP, Brazil; e-mail: lanchote{at}fcfrp.usp.br.


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