THE EFFECTS OF CIMETIDINE, RANITIDINE AND FAMOTIDINE ON THE SINGLE-DOSE PHARMACOKINETICS OF NAPROXEN AND ITS METABOLITES IN HUMANS

We studied the effects of cimetidine, ranitidine and famotidine on the kinetics of naproxen. The mean t1/(2) beta of naproxen in 6 subjects was 25.7 +/- 5.4 h (range 16 to 36). Naproxen acyl glucuronide account s for 50.9 +/- 6.9% of the dose, its isomerized isoglucuronide for 6.8 +/- 2.6%, O-desmethylnaproxen acyl glucuronide for 14.3 +/- 4.1% and its isoglucuronide for 5.5 +/- 1.5% (n = 6). Naproxen (1.3 +/- 1.1%) a nd O-desmethylnaproxen (0.6 +/- 0.4%) are excreted in negligible amoun ts. Cimetidine, ranitidine and famotidine all reduced significantly th e t1/(2 beta) of naproxen by 50% from 25 h to 13 h and the t1/(2 alpha ) from 4.0 h to 1.1 h. No effect of the H-2 antagonists was observed o n the absorption of naproxen. They also reduced the V(ss)proxen by 50% . The amount of naproxen acyl glucuronide, naproxen isoglucuronide and O-desmethylnaproxen acyl glucuronide excreted in the urine, remained unchanged, 60%, 7%, and 14% respectively.