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.

Pharmacokinetic Considerations in the Treatment of Childhood Epilepsy

“…[57] enteral feedings has been recognized for over a decade. [53,54] Since the elimination half-life of phenytoin is concentration-dependent, when absorption is impeded with enteral or infant feedings main-…”

Guidelines for Drug Administration During Enteral Feeding

“…19 A study by Krueger et al indicated that the extent of absorption of phenytoin suspension after single doses was not altered by hourly or 4-hourly administration of Ensure. 20 They postulated that factors other than direct contact between enteral feeds and drug contribute to the decreased bioavailability of phenytoin. Randall and Tett studied intravenous phenytoin use in patients receiving long-term enteral feeding and suggested that the low concentrations of phenytoin observed clinically appeared to be due to increased clearance of the drug and not decreased bioavailability.…”

“…z Administering medications or nutrient solutions can clog tubes, with the incidence varying from 2% to 9%. 1 The preferred method for tube feeding in hospital is a continuous drip over [12][13][14][15][16][17][18][19][20][21][22][23][24] hours, usually by an infusion pump, as it reduces complications such as pulmonary aspiration and diarrhoea. If continuous drip feedings have been well tolerated, then bolus feeds can be used as long as the feeding tube is placed in the stomach -the stomach acts as a reservoir and delivers tolerable amounts of formula to the intestines.…”

Neuropharmacology and Drug Interactions in Clinical Practice

“…Addition of an inhibitor also causes concentrations to increase. Common agents that affect drug absorption, distribution, and metabolism are listed in Table 6. A significant clinical interaction involving ab- sorption occurs with PHT and enteral feeding formulas (Bauer, 1982;Krueger et al, 1987;Nishimura et al, 1988). In one study (Bauer, 1982), addition of Isocal continuous feeding via a nasogastric tube for 7 days significantly decreased mean PHT concentrations from 9.8 to 2.72 pg/ml.…”