title: Stereoselective analysis of metoprolol and its metabolites in rat plasma with application to oxidative metabolism.
abstract: We investigated the stereoselective kinetic disposition and metabolism of metoprolol (MET) in rats. The racemic MET (15 mg/kg) was given by oral gavage and blood samples were collected from 0 to 10h (n=6 at each time point). The enantiomeric concentrations of MET and its metabolites alpha-hydroxymetoprolol (alpha-OHM) and O-demethylmetoprolol (ODM) were determined by HPLC using a Chiralpak AD chiral column and fluorescence detection. The pharmacokinetic parameters of unchanged MET and the formation of ODM did not show to be stereoselective. In contrast, the AUC (ng h/mL) of alpha-hydroxymetoprolol isomers were higher to I'R [638.2(525.2-706.2) for 1'R2R and 659.6(580.4-698.1) for 1'R,2S, mean, (95%CI)] than to I'S products [58.3(47.4-66.1) for 1'S,2R and 57.1(44.7-67.9) for 1'S,2S, mean, (95%CI)]. We conclude that the kinetic disposition of unchanged MET and the formation of ODM are not enantioselective in rats but the metabolism of alpha-OHM yields predominantly the 1'R-product.
authors: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, Campus da USP, 14040-903 Ribeirão Preto, SP, Brazil.
authors: Vanessa Bergamin
authors: VB
authors: Boralli
authors: Eduardo Barbosa
authors: EB
authors: Coelho
authors: Paula Macedo
authors: PM
authors: Cerqueira
authors: Vera Lucia
authors: VL
authors: Lanchote
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002942:Circular Dichroism; D006207:Half-Life; D008297:Male; D008790:Metoprolol / Q000031:analogs & derivatives / Q000097:blood* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013237:Stereoisomerism
chemical_list: D000319:Adrenergic beta-Antagonists; C029504:alpha-hydroxymetoprolol; C029502:O-demethylmetoprolol; D008790:Metoprolol