Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patientswith normal to severely impaired renal function

Objective: We studied the pharmacokinetics and pharmacodynamics of single a nd multiple doses of candesartan cilexetil 8 mg per day in hypertensive pat ients with different degrees of renal function impairment. Candesartan is a n angiotensin II subtype I (AT1) receptor antagonist that is administered o rally as candesartan cilexetil which is converted in the active compound. Methods: Twenty-three patients were included, divided into groups according to creatinine clearance (cr cl. group A > 60 nl.min(-1).73 m(-2), group B 30-60 ml.min(-l).1.73 m(-2) and group C 15-30 ml. min(-1).1.73 m(-2)). Results: Trough serum concentrations of candesartan were higher in group C compared with group A. The values did not increase after multiple dosing, i ndicating absence of accumulation. There was a significant negative correla tion between the area under the concentration-time curve extrapolated to ti me infinity (AUC(inf)) and the glomerular filtration rate (GFR) indicating a lower renal clearance of candesartan in patients with impaired renal func tion. The onset of haemodynamic and hormonal effects was gradual. During th e single-dose study blood pressure as well as plasma renin activity (PRA) a nd angiotensin II were unchanged at peak. At day 5 of the multiple-dose stu dy blood pressure was lower and both PRA and angiotensin II were higher com pared with baseline. Conclusion: Although serum trough levels increased during repeated administ ration and half-lift: was higher in patients with impaired renal function, candesartan cilexetil at a dose of 8 mg per day does not lead to drug accum ulation in these patients. This dose is effective in lowering blood pressur e and appears to be suitable for patients with renal function impairment.