Pharmacokinetics and antihypertensive effects of candesartan cilexetil in patients undergoing haemodialysis: an open-label, single-centre study.
OBJECTIVE
In patients with endstage renal failure (ERF), activation of the renin-angiotensin-aldosterone system plays an important role in the onset and maintenance of arterial hypertension. This study aimed to elucidate the antihypertensive effect, pharmacokinetics and safety of candesartan cilexetil in patients with ERF undergoing haemodialysis.


METHODS
In 14 anuric hypertensive patients undergoing haemodialysis (mean+/- SD 24-hour systolic [SBP]/diastolic [DBP] blood pressure [BP] 142.9 +/- 11.1/75.0 +/- 10.1 mmHg), 24-hour BP measurements on the second interdialysis day per week were performed at baseline and at weeks 4, 12 and 24. All patients started antihypertensive treatment with candesartan cilexetil 4 mg once daily immediately before the start of haemodialysis. Subsequently, the dose was titrated upward to 8 mg once daily until the patient's mean ambulatory BP measurement (ABPM) values were <130/80 mmHg. Plasma candesartan pharmacokinetics were investigated on days 7 and 14 after starting candesartan cilexetil treatment and after each titration step.


RESULTS
After 6 months all patients demonstrated well controlled BP (ABPM mean +/- SD SBP 129.6 +/- 21.7/DBP 69.4 +/- 10.4 mmHg) and a significantly reduced pulse pressure (from a mean +/- SD 67.9 +/- 13.7 mmHg at baseline to a mean +/- SD 60.2 +/- 14.7 mmHg at 6 months), without any adverse events. Candesartan plasma concentrations increased over 3 hours followed by a continuous decline. Plasma concentrations remained stable after 7 and 14 days, independent of dosing. However, administration of candesartan cilexetil 8 mg (five patients) resulted in plasma concentrations about 1.4 times higher than those for candesartan cilexetil 4 mg.


CONCLUSIONS
In this study with small number of patients with ERF undergoing haemodialysis, candesartan cilexetil was effective in lowering BP and pulse pressure without accumulation or associated adverse effects such as elevated potassium or symptomatic hypotension.
Schulz
Egbert Godehard
EG
Centre of Nephrology Goettingen, Goettingen, Germany. eg.schulz@goedia.de
Bahri
Shadfar
S
Schettler
Volker
V
Popov
Aron-Frederik
AF
Hermann
Matthias
M
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D013777:Tetrazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C077793:candesartan cilexetil