The pharmacokinetics and pharmacodynamics of irbesartan in heart failure

Alterations in the pharmacokinetic parameters of a number of medications ha ve been observed inpatients with heart failure. Because the angiotensin II receptor antagonist irbesartan has beneficial effects in patients with hear t failure, the pharmacokinetics and pharmacodynamics of irbesartan in 10 pa tients with New York Heart Association (NYHA) class II or HI heart failure compared with 10 control subjects matched with respect to race, age, weight , and sex were studied. In a crossover study, participants were randomized to receive open-label irbesartan 75 mg as either an oral capsule or an intr avenous (IV) infusion in the first treatment period. After a 7- to 10-day w ashout period, participants were crossed over to the other treatment arm. S ingle-dose noncompartmental pharmacokinetic parameters, angiotensin II leve ls, and plasma renin activity (PRA) of irbesartan were determined for each participant. Following oral and IV administration, the pharmacokinetics of irbesartan in patients with heart failure was not significantly different f rom those of matched controls, indicating that there is little influence of potential changes in organ/tissue perfusion and gut edema on the absorptio n, distribution, and elimination of irbesartan. After dosing with irbesarta n, mean increases in angiotensin II and PRA concentrations were higher in p atients with heart failure than in the matched controls, but there was more interpatient variability in the patients with heart failure. Given the var iability of the data, no definitive conclusions can be made with regard to these pharmacodynamic parameters. The results of this study indicate that t he pharmacokinetics of irbesartan following oral and IV administration is n ot altered in patients with heart failure. Therefore, this indicates that n o dosage adjustment is needed when prescribing irbesartan in heart failure patients. (C) 2001 the American College of Clinical Pharmacology.