Irbesartan, pharmacokinetics

Brunner HR. The new angiotensin II receptor antagonist, irbesartan Pharmacokinetic and pharmacodynamic considerations. Am J Hypertens 1997 10 311S-17S. 

Structural differences of ARBs influence the variation in pharmacological (pharmacokinetic /pharmacodynamic) properties of these drugs. Affinity for the ATj receptor is highest with candesartan, followed by irbesartan, losartan, valsartan, and telmisartan. Differences and affinities at the ATj receptor are also involved in... 

Huang XH, Qiu FR, Xie HT, Li J. 2005. Pharmacokinetic and pharmacodynamic interaction between irbesartan and hydrochlorothiazide in renal hypertensive dogs. J Cardiovasc Pharmacol 46 863-869. 

A small well-designed study in 14 healthy subjects showed no significant effect of irbesartan on the single-dose pharmacokinetics of total simvastatin acid (7). 

Marino MR, VachharajaniNN, HadjUambris OW. Irbesartan does not affect the pharmacokinetics of simvastatin in healthy subjects. J Clin Pharmacol 2000 40(8) 875-9. 

Marino MIR, Vachharajani NN. Drug interactions with irbesartan. Clin Pharmacokinet (2001) 40, 605-14. 

Fluconazole reduces the conversion of losartan to its active metabolite and decreases the metabolism of irbesartan, but the clinical relevance of these changes is uncertain. Fluconazole does not appear to influence the pharmacokinetics of eprosartan cande-sartan and valsartan. Itraconazole does not significantly affect the pharmacokinetics or antihypertensive effects of losartan, and ketoconazole does not affect the pharmacokinetics of eprosartan or losartan. 

No significant pharmacokinetic interactions occur between nifedipine and candesartan or irbesartan, or between amlodipine and telmisartan or valsartan. Calcium-channel blockers have been given safely with eprosartan or irbesartan. 

Marino MR, Hammett JL, Ferreira I, Ford NF, Uderman HD. Effect of nifedipine on the steady-state pharmacokinetics and pharmacodynamics of irbesartan in healthy subjects. JCar-diovasc Pharmacol F/jer (1998) 3, 111-17. 

Symptomatic hypotension may occur when an angiotensin II receptor antagonist is started in patients taking high-dose diuretics. Potassium levels may be either increased, decreased or not affected. No clinically relevant pharmacokinetic interactions appear to occur between candesartan, eprosartan, irbesartan, losartan, telmisartan or valsartan and hydrochlorothiazide, although the bioavailability of hydrochlorothiazide may be modestly reduced. Similarly, there is no clinically significant pharmacokinetic interaction between valsartan and furosemide. 

In a randomised, crossover study in 13 healthy subjects, telmisartan 160 mg daily was given with hydrochlorothiazide 25 mg daily for 7 days. There was no difference in AUC and maximum plasma concentrations of either drug compared with when they were given alone. Similarly, no pharmacokinetic interactions were found between irbesartan and hydrochlorothiazide. ... 

Warfarin 2.5 to 10 mg daily was given to 16 healthy subjects for 2 weeks, with irbesartan 300 mg or a placebo daily for a further week. There was no evidence that irbesartan affected the pharmacokinetics or pharmacodynamics of warfarin. ... 

Mangold B, Gielsdorf W, Marino MR. Irbesartan does not affect the steady-state pharmacodynamics and pharmacokinetics of warfarin. EurJ Clin Pharmacol ( 999) 55, 593-8. 

Glibenclamide (glyburide) causes a small reduction in valsartan plasma levels, but this is unlikely to be of any clinical significance. No clinically relevant pharmacokinetic interaction occurs between glibenclamide and candesartan or tehnisartan, or between tolbutamide and irbesartan. Eprosartan does not alter the efficacy of glibenclamide. Losartan and possibly eprosartan may reduce awareness of hypoglycaemic symptoms. 

Candesartan, eprosartan, irbesartan, losartan, and valsartan do not appear to affect the pharmacokinetics of digoxin, but tel-misartan may cause a rise in serum digoxin levels. 

Irbesartan and telmisartan appear not to alter the pharmacokinetics of simvastatin, fluvastatin does not alter the pharmacokinetics of losartan or its active metabolite, and ohnesartan appears not to interact with pravastatin. 

A study in 12 healthy subjects found that irbesartan 300 mg had no significant effect on the pharmacokinetics of a single 50-mg dose of simvastatin, or its metabolite simvastatin acid, and the combination was well-tolerated. No clinically relevant interaction was noted when telmisartan was given with simvastatin. ... 

Tetrazole derivatives are frequently used as metabolically stable surrogates for carboxylic acids (due to bioisosterism, cf. p. 274), as tetrazoles generally offer a more favorable pharmacokinetical profile [541]. Incorporation of tetrazole functionalities is especially found in antihypertensives (angiotensin II antagonists) of the sartan family, for example, irbesartan (37), losartan (38), and valsartan (39) [542] ... 

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