Pharmacokinetics of prenalterol after single and multiple administration of controlled release tablets to patients with congestive heart failure.

Abstract

The pharmacokinetics of prenalterol, a partial β-adrenoceptor agonist, has been studied in 12 patients with congestive heart failure, following single and repeated oral doses of 40 mg b.i.d. as controlled release tablets. A tracer dose of3H-labelled drug was given i.v. on 2 occasions to establish the variability of the pharmacokinetic parameters. Plasma levels and urinary excretion of prenalterol were measured after the oral and intravenous doses, and in addition, total radioactive metabolites were determined after the i.v. administration. Only small differences in the pharmacokinetics were observed when the i.v. tracer dose was given with the single oral dose or with the oral maintenance dose at steady state. The mean plasma elimination half-life was 2.4 h, the apparent volume of distribution 2.61/kg and the total body clearance about 800 ml/min. About 90% of the dose was excreted in urine, of which 30% was the parent drug. The remaining fraction comprised three metabolites, which were quantified by HPLC. Plasma levels of prenalterol close to steady state were obtained within 2 days and were maintained on a b.i.d. dosage regimen with controlled release tablets. The levels were independent of whether the tablets were taken fasting or with a standardized light meal. An average of 14% of the oral dose was recovered as prenalterol in urine after a single dose and 16% after a maintenance dose at steady state. Thus, about 45–55% of prenalterol reached the systemic circulation. The pharmacokinetic parameters in patients with congestive heart failure differed slightly from those in healthy subjects, but not sufficiently to require a change in the oral dosage regimen.