Pharmacokinetics of famotidine in man

Famotidine (F) is an effective new H2-receptor antagonist. Knowledge of its pharmacokinetic properties and metabolism is scanty. Therefore, we investigated the disposition of F in 6 healthy male volunteers following a single oral (40 mg) and intravenous (20 mg) dose. F and a metabolite were monitored in plasma or urine by a HPLC method. After intravenous administration plasma levels declined biexponentially with an initial half-life (t1/2) of 0.5 h and a terminal t1/2 of 4.0 h. F was slightly bound to plasma proteins (less than 1 to 15%) and its distribution volume averaged 1.13 l/kg. About 72% of the dose could be recovered as unchanged F in urine. Thus, hepatic clearance contributes to the total plasma Cl of 309 ml/min only 88 ml/min. Consequently, a high hepatic first-pass effect can be excluded. Following oral administration maximum plasma concentrations of 104 +/- 39 ng/ml (mean +/- SD) were observed after 2.3 +/- 1 h. F was eliminated with a t1/2 of 3.6 +/- 1.1 h and its absolute bioavailability ranged from 20 to 66%. In urine an oxidized metabolite could be identified which accounts to about 2% of the given dose. In conclusion, F is rapidly eliminated mainly by the renal route and its t1/2 is slightly longer than those of other available H2-receptor antagonists.