Mathematical analysis of a phenytoin--disulfiram interaction

A case of phenytoin-disulfiram drug interaction is analyzed with a mathematical technique used in enzyme kinetics. Serum anticonvulsant levels, obtained before, during, and after disulfiram administration, were collected from hospital records retrospectively. Phenytoin kinetic constants--maximal velocity of metabolism (Vmax) and Michaelis-Menten constant (km)--before, during, and after disulfiram administration, were compared. The slopes (km) of the regression lines analyzed by a small sample t test for parallelism were not significantly different (p greater than 0.05). Y-intercept (Vmax) values obtained before (433 mg/day) and after (463 mg/day) disulfiram are both significantly different when compared with the y-intercept during (264 mg/day) disulfiram administration, by a small-sample t test for common intercept (p less than 0.05). Changes in the elimination rate of phenytoin or changes in y-intercept result from noncompetitive drug effects. It is concluded that disulfiram affects phenytoin's elimination rate by noncompetitive mechanisms.