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1. In a double‐blind crossover study 10 healthy males received either placebo or omeprazole (40 mg day‐1) for 9 days, a single dose of phenytoin (300 mg) being taken on the seventh day. 2. Omeprazole significantly increased the area under the curve (0 to 72 h) of phenytoin (mean +/‐ s.e. mean) from 121.6 +/‐ 14.0 to 151.4 +/‐ 13.6 micrograms ml‐1 h) (P less than 0.01). 3. The peak concentration, and apparent elimination half‐life of phenytoin also tended to be increased though not significantly. 4. The omeprazole‐phenytoin interaction observed may be clinically important because of the low therapeutic index associated with phenytoin.

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