Plasma tolbutamide half-life was measured in nine previously untreated mature onset diabetics before and after a minimum of two weeks treatment with 1.0 to 1.5 gm. of tolbutamide daily. The tolbutamide half-life was shortened in six patients, but the mean reduction in mean half-life from 5.7 to 5.3 hours was not statistically significant. Five patients then took phenobarbital, 60 to 90 mg. daily, for two weeks. There was no further reduction in mean tolbutamide half-life. Self-induced stimulation of tolbutamide metabolism is unlikely to be an important factor in the secondary failure of treatment of diabetics with this drug.
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