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

We studied the pharmacokinetics and pharmacodynamics of single and multiple doses of candesartan cilexetil 8 mg per day in hypertensive patients with different degrees of renal function impairment. Candesartan is an angiotensin II subtype 1 (AT1) receptor antagonist that is administered orally as ca...

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Bibliographic Details
Published in:	European journal of clinical pharmacology Vol. 54; no. 12; pp. 953 - 958
Main Authors:	BUTER, H, NAVIS, G. Y, WOITTIEZ, A. J. J, DE ZEEUW, D, DE JONG, P. E
Format:	Journal Article
Language:	English
Published:	Heidelberg Springer 01-02-1999 Berlin Springer Nature B.V
Subjects:	Adult Angiotensin II - blood Angiotensin II - drug effects Angiotensin Receptor Antagonists Antihypertensive agents Antihypertensive Agents - administration & dosage Antihypertensive Agents - pharmacokinetics Antihypertensive Agents - pharmacology Benzimidazoles - administration & dosage Benzimidazoles - blood Benzimidazoles - pharmacokinetics Benzimidazoles - pharmacology Biological and medical sciences Biphenyl Compounds - administration & dosage Biphenyl Compounds - pharmacokinetics Biphenyl Compounds - pharmacology Blood pressure Blood Pressure - drug effects Cardiovascular system Female Humans Hypertension - complications Kidney - physiopathology Kidney Diseases - metabolism Kidney Diseases - physiopathology Kidneys Male Medical research Medical sciences Middle Aged Pharmacology. Drug treatments Prodrugs - administration & dosage Prodrugs - pharmacology Renin - blood Renin - drug effects Tetrazoles - blood Human Hypertension Kidney disease Pharmacokinetic pharmacodynamic relationship Cilexetil Urinary system disease Renal function Candesartan Metabolite Treatment efficiency Single dose Oral administration Cardiovascular disease Multiple dose Concomitant disease Chemotherapy Antihypertensive agent Angiotensin antagonist Angiotensin II Pharmacokinetics Biological receptor
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Summary:	We studied the pharmacokinetics and pharmacodynamics of single and multiple doses of candesartan cilexetil 8 mg per day in hypertensive patients with different degrees of renal function impairment. Candesartan is an angiotensin II subtype 1 (AT1) receptor antagonist that is administered orally as candesartan cilexetil which is converted in the active compound. Twenty-three patients were included, divided into groups according to creatinine clearance (cr cl. group A >60 nl x min(-1) x 1.73 m(-2), group B 30-60 ml x min(-1) x 1.73 m(-2) and group C 15-30 ml x min(-1) x 1.73 m(-2)). Trough serum concentrations of candesartan were higher in group C compared with group A. The values did not increase after multiple dosing, indicating absence of accumulation. There was a significant negative correlation between the area under the concentration-time curve extrapolated to time infinity (AUCinf) and the glomerular filtration rate (GFR) indicating a lower renal clearance of candesartan in patients with impaired renal function. The onset of haemodynamic and hormonal effects was gradual. During the single-dose study blood pressure as well as plasma renin activity (PRA) and angiotensin II were unchanged at peak. At day 5 of the multiple-dose study blood pressure was lower and both PRA and angiotensin II were higher compared with baseline. Although serum trough levels increased during repeated administration and half-life was higher in patients with impaired renal function, candesartan cilexetil at a dose of 8 mg per day does not lead to drug accumulation in these patients. This dose is effective in lowering blood pressure and appears to be suitable for patients with renal function impairment.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0031-6970 1432-1041
DOI:	10.1007/s002280050581