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Guangdong candesartan ester of pharmacology and toxicology pharmacokinetics

Pharmacology and toxicology 】 【 guangdong candesartan ester in the body quickly be hydrolyzed into active metabolite candesartan, candesartan for selective angiotensin Ⅱ (AT1) receptor antagonist, by combined with vascular smooth muscle of AT1 receptor antagonist of angiotensin Ⅱ vasoconstriction, reducing peripheral vascular resistance. Another thought: candesartan can inhibit the adrenal glands secrete aldosterone and play a certain antihypertensive effect. Guangdong candesartan ester not restrain excited peptidase Ⅱ, does not affect the slow shock peptide degradation. Experiments show that: in patients with high blood pressure patients take this product many times can cause plasma renin activity and angiotensin 1 concentration and angiotensin Ⅱ concentration increased; This product for 2-8 mg once daily, can make the systolic pressure, diastolic pressure drops, left ventricular myocardial weight, peripheral vascular resistance decreased, and the central discharge, ejection fraction, renal vascular resistance, renal blood flow and glomerular filtration rate has no obvious influence; For primary natural disposition is hypertension patients with cerebrovascular disorders, for had no effect on cerebral blood flow.

Guangdong pharmacokinetic 】 【 candesartan ester is a precursor of candesartan medicine, in the gastrointestinal tract absorption is quickly and completely during hydrolysis of candesartan, absolute bioavailability of candesartan is about 15%, the concentration of plasma candesartan tmax for 3-4 hours. The combination of candesartan and plasma protein rate is greater than 99%, the distribution of apparent volume of 0.13 L/kg. Rat experiments show that candesartan rarely through the blood brain barrier, but through the placental barrier and distribution to the tire. Candesartan in prototype mainly by the urinary and fecal excretion, few in the liver by 0 - to generate inactive metabolites ethylation reaction. The elimination of the guangdong candesartan ester half-life of about nine hours. High blood pressure in patients with oral 2 to 16 mg/day, 4 weeks continuous administration, candesartan plasma clearance of 14.07 L/h, terminal elimination half-life of 9-13 hours. The data shows, the total clearance of candesartan is 0.37 ml/min · kg, renal clearance is 0.19 ml/min, kg. Oral 14 c guangdong candesartan ester, recovery of 33% and 33% respectively in the urine, dung radioactivity.

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