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| __NOTOC__
| | #REDIRECT [[Irbesartan#Pharmacology]] |
| {{Irbesartan}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Clinical Pharmacology==
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| ===Pharmacokinetics===
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| Irbesartan is an orally active agent that does not require biotransformation into an active form. The oral absorption of irbesartan is rapid and complete with an average absolute bioavailability of 60% to 80%. Following oral administration of AVAPRO, peak plasma concentrations of irbesartan are attained at 1.5 to 2 hours after dosing. Food does not affect the bioavailability of AVAPRO.
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| Irbesartan exhibits linear pharmacokinetics over the therapeutic dose range.
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| The terminal elimination half-life of irbesartan averaged 11 to 15 hours. Steady-state concentrations are achieved within 3 days. Limited accumulation of irbesartan (<20%) is observed in plasma upon repeated once-daily dosing.
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| ===Metabolism and Elimination===
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| Irbesartan is metabolized via glucuronide conjugation and oxidation. Following oral or intravenous administration of 14C-labeled irbesartan, more than 80% of the circulating plasma radioactivity is attributable to unchanged irbesartan. The primary circulating metabolite is the inactive irbesartan glucuronide conjugate (approximately 6%). The remaining oxidative metabolites do not add appreciably to irbesartan's pharmacologic activity.
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| Irbesartan and its metabolites are excreted by both biliary and renal routes. Following either oral or intravenous administration of 14C-labeled irbesartan, about 20% of radioactivity is recovered in the urine and the remainder in the feces, as irbesartan or irbesartan glucuronide.
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| In vitro studies of irbesartan oxidation by cytochrome P450 isoenzymes indicated irbesartan was oxidized primarily by 2C9; metabolism by 3A4 was negligible. Irbesartan was neither metabolized by, nor did it substantially induce or inhibit, isoenzymes commonly associated with drug metabolism (1A1, 1A2, 2A6, 2B6, 2D6, 2E1). There was no induction or inhibition of 3A4.
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| ===Distribution===
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| Irbesartan is 90% bound to serum proteins (primarily albumin and α1-acid glycoprotein) with negligible binding to cellular components of blood. The average volume of distribution is 53 liters to 93 liters. Total plasma and renal clearances are in the range of 157 mL/min to 176 mL/min and 3.0 mL/min to 3.5 mL/min, respectively. With repetitive dosing, irbesartan accumulates to no clinically relevant extent.
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| Studies in animals indicate that radiolabeled irbesartan weakly crosses the blood-brain barrier and placenta. Irbesartan is excreted in the milk of lactating rats.
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| ===Special Populations===
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| ====Gender====
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| No gender-related differences in pharmacokinetics were observed in healthy elderly (age 65–80 years) or in healthy young (age 18–40 years) subjects. In studies of hypertensive patients, there was no gender difference in half-life or accumulation, but somewhat higher plasma concentrations of irbesartan were observed in females (11–44%). No gender-related dosage adjustment is necessary.
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| ====Geriatric====
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| In elderly subjects (age 65–80 years), irbesartan elimination half-life was not significantly altered, but AUC and Cmax values were about 20% to 50% greater than those of young subjects (age 18–40 years). No dosage adjustment is necessary in the elderly.
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| ====Race====
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| In healthy black subjects, irbesartan AUC values were approximately 25% greater than whites; there were no differences in Cmax values.
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| ====Renal Insufficiency====
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| The pharmacokinetics of irbesartan were not altered in patients with renal impairment or in patients on [[hemodialysis]]. Irbesartan is not removed by [[hemodialysis]]. No dosage adjustment is necessary in patients with mild to severe [[renal impairment]] unless a patient with renal impairment is also volume depleted. (See WARNINGS: Hypotension in Volume- or Salt-Depleted Patients and DOSAGE AND ADMINISTRATION.)
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| ====Hepatic Insufficiency====
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| The pharmacokinetics of irbesartan following repeated oral administration were not significantly affected in patients with mild to moderate cirrhosis of the liver. No dosage adjustment is necessary in patients with [[hepatic insufficiency]].
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| ===Pharmacodynamics===
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| In healthy subjects, single oral irbesartan doses of up to 300 mg produced dose-dependent inhibition of the pressor effect of [[angiotensin]] II infusions. Inhibition was complete (100%) 4 hours following oral doses of 150 mg or 300 mg and partial inhibition was sustained for 24 hours (60% and 40% at 300 mg and 150 mg, respectively).
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| In hypertensive patients, [[angiotensin]] II receptor inhibition following chronic administration of irbesartan causes a 1.5- to 2-fold rise in [[angiotensin]] II plasma concentration and a 2- to 3-fold increase in plasma renin levels. Aldosterone plasma concentrations generally decline following irbesartan administration, but serum potassium levels are not significantly affected at recommended doses.
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| In hypertensive patients, chronic oral doses of irbesartan (up to 300 mg) had no effect on glomerular filtration rate, renal plasma flow, or filtration fraction. In multiple dose studies in hypertensive patients, there were no clinically important effects on fasting [[triglyceride]]s, total [[cholesterol]], HDL-[[cholesterol]], or fasting glucose concentrations. There was no effect on serum uric acid during chronic oral administration, and no uricosuric effect.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = AVAPRO (IRBESARTAN) TABLET [SANOFI-AVENTIS U.S. LLC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=7885b2a8-be4e-48ab-8113-4e6ab791eb98 | publisher = | date = | accessdate = 20 February 2014 }}</ref>
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| ==References==
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| {{Reflist}}
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| {{Angiotensin II receptor antagonists}}
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| [[Category:Angiotensin II receptor antagonists]]
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| [[Category:Sanofi]]
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| [[Category:Bristol-Myers Squibb]]
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| [[Category:Tetrazoles]]
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| [[Category:Biphenyls]]
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| [[Category:Lactams]]
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| [[Category:Spiro compounds]]
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| [[Category:Nitrogen heterocycles]]
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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