Clinical profile of the novel angiotensin II type I blocker candesartan cilexetil.
PROPERTIES OF CANDESARTAN CILEXETIL: Candesartan is a novel, potent, highly selective antagonist of the angiotensin II receptor subtype 1, which is administered orally as candesartan cilexetil, and is rapidly and completely hydrolysed into candesartan, the active moiety, during absorption in the intestinal tract. At a dose of 4-16 mg once a day, candesartan cilexetil significantly lowers systolic and diastolic blood pressure in a clear dose-dependent fashion, with 16 mg showing the greatest effect. This blood pressure fall is sustained throughout the 24-h period, as shown by a trough to peak ratio in excess of 80%, across all doses. The recommended maintenance dose for first-line monotherapy in patients with essential hypertension is 8 or 16 mg.
In controlled, well designed, clinical trials involving more than 5000 subjects with mild to moderate hypertension, candesartan cilexetil at 4-8 mg was as effective as enalapril at 10-20 mg. At 8 mg, candesartan cilexetil was as effective as 50 mg losartan, and also showed equivalent efficacy to 5 mg amlodipine and 25 mg hydrochlorothiazide. In addition, candesartan cilexetil has an additive antihypertensive effect when used in combination with amlodipine or hydrochlorothiazide, also when tested in patients with severe hypertension. ADVERSE-EVENT PROFILE: The adverse-event profile with candesartan cilexetil was similar to that with placebo, with no evidence of dose-dependent adverse events. The drug was equally well tolerated by men and women and by elderly (> or = 65 years) and younger (< 65 years) patients alike.


CONCLUSIONS
Effective and sustainable blood pressure control in patients with essential hypertension can be achieved with candesartan cilexetil in doses of 8 or 16 mg once a day without drug-related adverse events. This agent is therefore a promising alternative to established modern antihypertensive agents.
Sever
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Department of Clinical Pharmacology, Imperial College of Science, Technology and Medicine, St Mary's Hospital, London, UK.
D000284:Administration, Oral; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012449:Safety; D013777:Tetrazoles; D016896:Treatment Outcome
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; C077793:candesartan cilexetil