BIOAVAILABILITY OF PHENYTOIN ACID AND PHENYTOIN SODIUM WITH ENTERAL FEEDINGS

Study Objective. To compare the absolute bioavailability of phenytoin (PHT) sodium solution and PHT acid suspension in healthy volunteers re ceiving continuously infused enteral feedings. Design. Randomized, ope n-label, single-dose, three-period crossover study. Setting. Universit y clinical research center. Subjects. Ten healthy volunteers age 23-43 years. Interventions. The three phases of the study were separated by at least 7 days. During phase A, subjects received PHT sodium 435 mg intravenously over 30 minutes. During phases B and C, subjects had a n asogastric feeding tube placed through which PHT acid suspension 400 m g and PHT sodium solution 435 mg were administered, respectively. For phases B and C, continuous enteral feedings were given by feeding tube for 14 hours before and after the PHT dose. Blood samples were collec ted over 72 hours after each PHT dose, and the serum was analyzed for PHT. Measurements and Main Results. The rate and extent of PHT absorpt ion and PHT pharmacokinetics were determined using an empirical quadra tic function of time method. Bioavailability, rate of absorption, maxi mum concentration (C-max), and time to maximum concentration (T-max) w ere compared for the two enteral doses by paired Student's t test. The re were no significant differences in bioavailability for PHT acid sus pension and PHT sodium solution (0.88 +/- 0.15 vs 0.91 +/- 0.7, p=0.57 , 90% CI -0.14-0.071). The C-max was greater (7.4 +/- 0.9 mg/L vs 5.5 +/- 1.7 mg/L, p=0.019) and T-max was less (2.5 +/- 3.8 vs. 14.8 +/- 11 .2 hrs, p=0.004) for the sodium solution. The time to 50% fractional a bsorption (0.33 +/- 0.08 vs 3.2 +/- 2.4 hrs, p=0.004) and 90% fraction al absorption (7.9 +/- 6.2 vs 22.3 +/- 17.2 hrs, p=0.021) was also sig nificantly shorter for the sodium solution. Conclusion. The absolute b ioavailability of the two dosage forms of PHT administered with concom itant enteral feedings were not significantly different, however, the absorption patterns were significantly different, with the sodium solu tion being more rapidly absorbed.