PHARMACOKINETICS OF TAMSULOSIN HYDROCHLORIDE IN PATIENTS WITH RENAL IMPAIRMENT - EFFECTS OF ALPHA(1)-ACID GLYCOPROTEIN

The pharmacokinetics of tamsulosin hydrochloride in patients with rena l impairment were compared with those in healthy volunteers, and the f actors that influenced plasma levels of tamsulosin were elucidated. A single oral dose of 0.2 mg of tamsulosin was given and blood and urine samples were obtained for 36 hours after administration. Unbound plas ma concentration of tamsulosin was measured by a combination of equili brium dialysis and liquid chromatography tandem mass spectrometry meth ods to examine the effect of protein binding on the pharmacokinetics o f tamsulosin. Mean values for maximum concentration (C-max) and area u nder the concentration-time curve (AUC) of total drug (C-max) and AUC( t)) in patients with renal impairment were 73% and 211% greater, respe ctively, than those in healthy volunteers. Mean C-max and AUC of unbou nd drug (C-max,C-u and AUC(u)), however, were almost the same in the t wo groups. A high correlation was found between alpha(1)-acid glycopro tein (alpha(1)-AGP) concentration and AUC(t), but no correlation was f ound between alpha(1)-AGP concentration and AUC(u,0-36), or between cr eatinine clearance (Cl-CR) and AUC(u,0-36). These results sh ow that i n patients with renal impairment, the pharmacokinetics of tamsulosin a re affected by the change in protein binding that is associated with a lteration of plasma alpha(1)-AGP concentration, but are not largely af fected by the decrease in the renal excretion. Although total tamsulos in levels increased as plasma protein binding increased, unbound tamsu losin levels (which are directly associated with the pharmacologic eff ects) remained unchanged in these patients.