Pharmacokinetic study of 14C-letosteine in man after oral intake and steady-state

Based on previous animal and on preliminary human results a further human study was performed in order to confirm the relevant pharmacokinetic parameters and the lack of accumulation of letosteine after repeated administrations. Thus, six healthy male volunteers were given a single oral dose of 50 mg (100 microCi) 14C-letosteine in form of gelatine capsules. A treatment lasting 11 days to obtain a steady-state was started three days later with three similar daily oral doses of unlabelled letosteine. Then, one capsule of 14C-letosteine was administered again. The radioactivity of blood, plasma, urine and expired air was measured at regular intervals after both radioactive doses. Several pharmacokinetic parameters were calculated for the single oral intake and for the oral intake at steady state. The results show a good absorption rate of letosteine since about 90% of the dose was found in the urine. Elimination was biphasic, with half-lives of about 1 and 4 hours in blood and plasma. No striking differences were recorded between the single oral intake and the oral intake at steady state for the various parameters assessed: Cmax, Tmax, AUC, Aeurine and AeCO2. It was therefore concluded that repeated doses of letosteine did not influence the absorption, the distribution, the metabolism and the elimination processes.