Interaction of ibuprofen with the H-2 receptor antagonists ranitidine and cimetidine

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Abstract
The influences of cimetidine and ranitidine on single-dose ibuprofen kinetics were evaluated. Thirteen healthy subjects took a single, 600 mg oral dose of ibuprofen on three occasions: in the control state without drug coadministration; during concurrent dosing with cimetidine, 1.2 gm/day; and during concurrent dosing with ranitidine, 150 mg twice daily. Compared with the control state, cimetidine increased the peak serum ibuprofen concentration (64 vs. 56 .mu.g/ml), but the value during ranitidine dosing (57 .mu.g/ml) was indistinguishable from the control value. There were no significant differences between control, cimetidine, and ranitidine conditions in ibuprofen elimination t1/2 (2.1, 2.1, and 2.0 hours, respectively). Overall there was a significant difference among the control, cimetidine, and ranitidine conditions in ibuprofen oral clearance (52.8, 48.3, and 54.1 ml/min, respectively), but individual differences in cimetidine vs. control and between ranitidine vs. control were not statistically significant. The impairment of ibuprofen clearance by cimetidine is small, and ranitidine had no detectable effect on ibuprofen kinetics. These findings should be further validated during chronic dosing with ibuprofen.