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Influence of H 2 Receptor Antagonists on the Disposition of Flurbiprofen Enantiomers
Author(s) -
PharmD Ralph E. Small,
Cox Steven R.,
Adams Wade J.
Publication year - 1990
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1990.tb01870.x
Subject(s) - flurbiprofen , cimetidine , ranitidine , metabolite , pharmacokinetics , pharmacology , chemistry , active metabolite , drug interaction , oral administration , enantiomer , crossover study , medicine , stereochemistry , biochemistry , placebo , alternative medicine , pathology
The effect of oral cimetidine or ranitidine on the pharmacokinetics of the R and S enantiomers of the nonsteroidal anti‐inflammatory drug flurbiprofen and its major metabolite, 4′‐hydroxyflurbiprofen, was evaluated. Nine healthy volunteers participated in a randomized crossover design study with the following treatments: (A) flurbiprofen 200 mg; (B) flurbiprofen 200 mg plus ranitidine 150 mg bid for 7 days before and for 2 days after receiving flurbiprofen and (C) flurbiprofen 200 mg plus cimetidine 300 mg qid for 7 days before and for 2 days after receiving flurbiprofen. Blood and urine samples were collected at various intervals during a 48‐hour period. These samples were assayed stereospecifically for flurbiprofen and its metabolite. Small but statistically significant differences in the terminal elimination rate constant (K), maximum peak serum drug concentration (C max ), time to reach peak concentration (t max ). oral clearance (Cl/F) and area under the curve (AUC) were noted for flurbiprofen enantiomers. No significant treatment*isomer interactions were observed, indicating that neither cimetidine nor ranitidine interacted stereospecifically with flurbiprofen. Cimetidine, but not ranitidine, resulted in small (≤15%) but statistically significant changes in flurbiprofen pharmacokinetic parameters. The interaction between H 2 ‐antagonists and flurbiprofen is unlikely to be clinically important.