The effects of cimetidine, ranitidine and famotidine on the single-dose pharmacokinetics of naproxen and its metabolites in humans

• Published in: International journal of clinical pharmacology, therapy, and toxicology Vol. 31; no. 12; p. 597
• Main Authors: Vree, T B, van den Biggelaar-Martea, M, Verwey-van Wissen, C P, Vree, M L, Guelen, P J
• Format: Journal Article
• Language: English
• Published: Germany 01-12-1993
• Subjects: Adult; Cimetidine - pharmacology; Drug Interactions; Famotidine - pharmacology; Female; Glucuronates - metabolism; Humans; Male; Middle Aged; Naproxen - metabolism; Naproxen - pharmacokinetics; Ranitidine - pharmacology
• ISSN: 0174-4879

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 accounts 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%) and O-desmethylnaproxen (0.6 +/- 0.4%) are excreted in negligible amounts. Cimetidine, ranitidine and famotidine all reduced significantly the 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 H2 antagonists was observed on the absorption of naproxen. They also reduced the Vss of naproxen 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.