The pharmacokinetics and pharmacodynamics of irbesartan in heart failure

Alterations in the pharmacokinetic parameters of a number of medications have been observed inpatients with heart failure. Because the angiotensin II receptor antagonist irbesartan has beneficial effects in patients with heart failure, the pharmacokinetics and pharmacodynamics of irbesartan in 10 patients 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 intravenous (IV) infusion in the first treatment period. After a 7- to 10-day washout period, participants were crossed over to the other treatment arm. Single-dose noncompartmental pharmacokinetic parameters, angiotensin II levels, 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 from those of matched controls, indicating that there is little influence of potential changes in organ/tissue perfusion and gut edema on the absorption, distribution, and elimination of irbesartan. After dosing with irbesartan, mean increases in angiotensin II and PRA concentrations were higher in patients with heart failure than in the matched controls, but there was more interpatient variability in the patients with heart failure. Given the variability of the data, no definitive conclusions can be made with regard to these pharmacodynamic parameters. The results of this study indicate that the pharmacokinetics of irbesartan following oral and IV administration is not altered in patients with heart failure. Therefore, this indicates that no dosage adjustment is needed when prescribing irbesartan in heart failure patients. (C) 2001 the American College of Clinical Pharmacology.