Effect of Two Administration Schedules of an Enteral Nutrient Formula on Phenytoin Bioavailability

Abstract

Continuous nasogastric (NG) administration of enteral nutrient formulas (ENFs) reportedly lowers phenytoin (PHT) concentrations. We studied the effects of two administration schedules of an ENF on the bioavailability of PHT. Eight healthy volunteers received 400 mg PHT suspension after fasting (A), with hourly Ensure (B), and with 4-hourly Ensure (C) in a randomized, crossover design. Data obtained from 13 serum samples collected over 80 h were analyzed using ESTRIP. Area under the serum concentration-time curve (AUC), time to maximum serum concentration (Tmax), and urinary excretion of 5-(p-hydroxyphenyl) 5-phenylhydantoin (HPPH) were compared by analysis of variance (ANOVA) and Bonferroni t tests of differences between means. AUCs (mg x h/L) were not different (p greater than 0.05) for A (222.1 +/- 86.9), B (233.9 +/- 92.9), and C (226.0 +/- 95.7). Tmax (h) was significantly shorter (p less than 0.05) when PHT was administered with Ensure (B = 8.5 +/- 3.0, C = 5.3 +/- 2.0) than without Ensure (A = 18.5 +/- 10.5). The HPPH excretion (mg/80 h) was not different (p greater than 0.05) for A (225.6 +/- 48.5), B (238.6 +/- 26.6), and C (229.9 +/- 45.6). Clearance and maximum concentration correlated with AUC, obviating the need for analysis. Relative bioavailability was B/A = 1.07 +/- 0.21, C/A = 1.01 +/- 0.14. The bioavailability of PHT was not decreased by either ENF administration schedule. Factors other than direct contact may be responsible for the observed decreases in PHT concentrations by coadministered ENFs.