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Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability
K A Krueger1, W R Garnett, T J Comstock
1Department of Pharmacy, School of Pharmacy, Virginia Commonwealth University, Medical College of Virginia, Richmond.
Insights
Enteral nutrient formulas (ENFs) do not decrease phenytoin (PHT) bioavailability, even with continuous or intermittent administration. This suggests other factors influence PHT concentration changes when given with ENFs.
Area of Science:
- Pharmacokinetics
- Drug-nutrient interactions
- Gastroenterology
Background:
- Continuous nasogastric administration of enteral nutrient formulas (ENFs) is reported to lower phenytoin (PHT) concentrations.
- The exact mechanism and impact on PHT bioavailability remain unclear.
Purpose of the Study:
- To investigate the effect of two different enteral nutrient formula (ENF) administration schedules on phenytoin (PHT) bioavailability.
- To determine if continuous or intermittent ENF administration affects PHT absorption and elimination.
Main Methods:
- A randomized, crossover study involving eight healthy volunteers.
- Administration of phenytoin (PHT) suspension after fasting, with hourly ENF, and with 4-hourly ENF.
- Analysis of serum samples over 80 hours for PHT concentrations, AUC, Tmax, and urinary HPPH excretion.
Main Results:
- Area under the serum concentration-time curve (AUC) for PHT was not significantly different across all administration groups (fasting, hourly ENF, 4-hourly ENF).
- Time to maximum serum concentration (Tmax) was significantly shorter when PHT was administered with ENF compared to fasting.
- Urinary excretion of 5-(p-hydroxyphenyl) 5-phenylhydantoin (HPPH) did not differ significantly between groups, indicating similar metabolic pathways.
Conclusions:
- Enteral nutrient formula (ENF) administration, whether continuous or intermittent, does not decrease phenytoin (PHT) bioavailability.
- The observed reductions in PHT concentrations with coadministered ENFs may be due to factors other than direct physical interactions affecting absorption.
- Further research is needed to elucidate the mechanisms behind PHT concentration changes when administered with ENFs.
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.