Evaluation of a nomogram for estimating the rate of phenytoin accumulation

This study evaluated a nomogram designed to identify a subgroup of the patients whose serum phenytoin concentrations are near steady state at a given time after initiation of therapy. A sample of 95 adult subjects with reported values of Vmax and Km was pooled from the literature, and computer simulations of phenytoin accumulation for 15 days after initiation of phenytoin acid at 300 mg/day were performed. Simulated serum concentrations on days 5, 10, and 15 were used to identify subjects who were predicted by the nomogram to be at greater than or equal to 83% of steady state, and these results were compared with those expected from the Michaelis-Menten model. In the simulations, 42, 62, and 66 subjects reached greater than or equal to 83% of steady state by days 5, 10, and 15, respectively. The nomogram correctly identified 13 (31.0%), 33 (53.2%), and 43 (65.2%) of these individuals, respectively. The frequency of erroneous predictions was low, even in subjects whose Km and volume of distribution were outside the limits set in the development of the nomogram. Use of a nomogram such as this would help a subgroup of patients to attain a desired serum phenytoin concentration earlier in therapy and with fewer serum phenytoin determinations than would otherwise be required. It would also prevent premature increases in phenytoin dose in patients whose serum concentration is still rising.