Pharmacokinetics of rilmenidine

Abstract

Rilmenidine is a novel antihypertensive agent related to alpha 2-adrenoceptor agonist, used in the treatment of mild or moderate hypertension at the oral dose of 1 mg once a day or 1 mg twice a day. The pharmacokinetic parameters were investigated after single or repeated administration in healthy subjects, using labeled and unlabeled compounds. Rilmenidine was rapidly and extensively absorbed, with an absolute bioavailability close to one and a time to peak plasma concentration of two hours. Rilmenidine was not subjected to presystemic metabolism. Distribution was independent of the free fraction since rilmenidine was weakly bound to plasma proteins (less than 10 percent). The volume of distribution was approximately 5 liters/kg (315 liters). Elimination was rapid, with a total body plasma clearance of approximately 450 ml/minute and an elimination half-life of approximately eight hours. Renal excretion was the major elimination process (two thirds of the total clearance); the parent drug in urine accounted for about 65 percent of the dose administered. Metabolism was very poor; few metabolites were found in urine and no metabolites were detected in plasma. Linear pharmacokinetics was demonstrated for rilmenidine from 0.5 to 2 mg; at 3 mg, a slight deviation from linearity was observed. In repeated administration, the linearity with dose of the pharmacokinetics of rilmenidine was confirmed.