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 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.
Vree
T B
TB
Department of Clinical Pharmacy, Academic Hospital Sint Radboud, Nijmegen, The Netherlands.
van den Biggelaar-Martea
M
M
Verwey-van Wissen
C P
CP
Vree
M L
ML
Guelen
P J
PJ
D000328:Adult; D002927:Cimetidine / Q000494:pharmacology*; D004347:Drug Interactions; D015738:Famotidine / Q000494:pharmacology*; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000378:metabolism / Q000493:pharmacokinetics*; D011899:Ranitidine / Q000494:pharmacology*
D005965:Glucuronates; D009288:Naproxen; D015738:Famotidine; D002927:Cimetidine; D011899:Ranitidine