PHARMACOKINETICS OF GLYCOPYRRONIUM IN UREMIC PATIENTS

We studied the pharmacokinetics of glycopyrronium in 11 uraemic patients undergoing cadaveric renal transplantation and in seven ASA I control patients undergoing general surgery. Glycopyrronium 4 mug kg-1 was given i.v. before induction of anaesthesia. Blood and urine samples were collected for up to 24 h for measurement of glycopyrronium concentrations using a radioreceptor assay. Volume of distribution in the elimination phase (V(beta)) was similar in both groups, the elimination half-life (T1/2beta) was longer (P < 0.05), area under the plasma concentration-time curve (AUC) larger (P < 0.01) and plasma clearance (Cl) smaller (P < 0.01) in the uraemic patients. In 3 h, mean 0.7 (range 0-3) % and 50 (21-82) % of glycopyrronium was excreted in the urine in the uraemic and healthy patients, respectively (P < 0.001). The 24-h renal excretion was 7 (0-25) % in uraemic and 65 (30-99) % in control patients (P < 0.001). We conclude that the elimination of glycopyrronium is severely impaired in uraemic patients.