THE PHARMACOKINETICS OF MOXONIDINE

After oral administration of an immediate release tablet or a solution , moxonidine is rapidly (t(max) around 1 h) and almost completely abso rbed from the upper gastrointestinal tract. The absolute bioavailabili ty of the oral dosage form is about 88%, indicating no significant fir st-pass metabolism. Two metabolites with very little pharmacodynamic a ctivity have been identified: dehydrogenated moxonidine, and the guani dine metabolite. They account for about 5-10% of the administered dose . The elimination of moxonidine and its metabolites is fairly rapid (t erminal hall-lives of approximately 2.5 h and 5 h, respectively) and o ccurs mainly via the renal route. About 60-80% of an orally administer ed moxonidine dose is excreted as unchanged drug into the urine. As re nal clearance for unbound moxonidine exceeds the glomerular filtration rate by about four to seven times, it is evident that active tubular secretion contributes significantly to the renal excretion. Plasma pro tein binding, as determined in vitro, was about 7.2%. Moxonidine passe s into maternal breast mirk, from which it is rapidly eliminated. Food intake has no influence on the pharmacokinetics of the drug, in hyper tensive patients, no relevant pharmacokinetic changes were observed co mpared to healthy subjects. Age-related changes in pharmacokinetics ha ve been observed and are most likely due to a reduced metabolic activi ty and/or slightly higher bioavailability in the elderly. However, the pharmacokinetic differences were not considered to be clinically rele vant. Renal impairment reduces the renal clearance of moxonidine, resu lting in increased AUC((0-24h)) and C-max values. As moxonidine treatm ent is based on individual dose titration no a priori dose adjustment in renally impaired patients seems to be necessary. Moxonidine does no t interact with hydrochlorothiazide, digoxin or moclobemide. A slight pharmacokinetic interaction was observed with glibenclamide but to suc h a small extent that it was not considered clinically relevant. A pha rmacodynamic interaction was observed with lorazepam, as coadministrat ion of lorazepam and moxonidine showed an impairment of cognitive func tioning greater than had been predicted considering the two compounds separately (but still of moderate magnitude).