CO-REGULATION OF PHENYTOIN AND TOLBUTAMIDE METABOLISM IN HUMANS

1 The disposition of phenytoin and tolbutamide was compared in eighteen healthy young adults separately administered single therapeutic doses (sodium phenytoin 300 mg, tolbutamide 500 mg) of the two drugs. 2 Within the group, ratios of ranges of total and unbound areas under the plasma concentration-time curves were similar for both drugs. 3 There were significant (P < 0.001) correlations between total (r = 0.88) and unbound (r = 0.86) areas under the plasma phenytoin and tolbutamide concentration-time curves. 4 The results are consistent with the involvement of the same cytochrome P-450 isoenzyme(s) in the metabolism of tolbutamide and phenytoin.