The effect of impaired renal function on the pharmacokinetics of metoprolol after single administration of a 14/190 metoprolol OROS system.
Renal function is known to sometimes have a significant effect on the pharmacokinetics of drugs or drug metabolites, which are eliminated in appreciable amounts by the kidneys. For this reason, we conducted a study to compare the plasma concentration profiles of metoprolol and its metabolite, alpha-hydroxymetoprolol (OH-metoprolol), in healthy volunteers and in renally impaired patients. Following a single oral dose of a 14/190 metoprolol OROS (oral osmotic) tablet, plasma metoprolol profiles were shown to be similar for both subject groups. However, in renally impaired patients, renal clearance of OH-metoprolol was reduced and mean plasma levels of OH-metoprolol were increased approximately two- to threefold in comparison with healthy volunteers. The accumulation of OH-metoprolol in plasma, however, is unlikely to contribute to the beta-blocking effect of metoprolol, since OH-metoprolol possesses only one tenth the activity of its parent compound.
Lloyd
P
P
CIBA-GEIGY Pharmaceuticals, Horsham, West Sussex, UK.
John
V A
VA
Signy
M
M
Smith
S E
SE
D000284:Administration, Oral; D003692:Delayed-Action Preparations; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000652:urine; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D009994:Osmolar Concentration
D003692:Delayed-Action Preparations; C029504:alpha-hydroxymetoprolol; D008790:Metoprolol