Effect of pH on the Equilibrium Dialysis of Phenytoin Suspension with and without Enteral Feeding Formula

Michele Y. Splinter, Charles F. Seifert, J. Chris Bradberry, Loyd V. Allen

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Significant decreases have been reported in phenytoin absorption when the suspension is combined with continuous enteral feedings. Several theories for this interaction have been proposed including binding of phenytoin to the protein constituents of the enteral formula, phenytoin binding to the calcium in the enteral formula, and inadequate dissolution of the suspension when delivered with the enteral formula due to the high pKa of phenytoin and the acidic nature of the enteral formula. We therefore evaluated the effects of pH levels 2.0, 3.5, 6.0, and 8.0 on the interaction of phenytoin suspension with enteral formula (Osmolite) with equilibrium dialysis using a Spectra/Por 1 (MWCO 6000-8000) molecularporous dialysis membrane. Phenytoin concentrations in the dialysis membrane (internal phase) mimicked the expected stomach concentrations of a 100-mg dose administered in an adult stomach containing 200 ml of gastric fluid. External phase buffers were sampled at 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, and 24.0 hr after the start of the dialysis. The phenytoin concentrations in the external phase were compared between buffer alone or buffer combined with enteral formula at the same pH and time intervals. With pH 2.0 and 3.5 the enteral formula formed an aggregate with suspension whereas no aggregate was formed with pH 6.0 and 8.0. The phenytoin concentrations with pH 2.0 were 26% to 44% lower and with pH 3.5 were 11.5 to 27% lower when phenytoin suspension was combined with enteral solution. However, at 24 hr there was no difference between the two conditions with both pH 2.0 and 3.5. With pH 6.0 there was a significant difference at 24 hr and with pH 8.0 significant differences were reached only at 0.5, 1.0 and 2.0 hr. These results show that the phenytoin suspension/enteral formula interaction is pH dependent. There appears to be a physical entrapment of the large suspension particles when the protein in the enteral solution denatures at lower pH's. These results may in part explain the decreased erratic absorption when phenytoin suspension is combined with enteral feedings. (Journal of Parenteral and Enteral Nutrition 14:275-278, 1990).

Original languageEnglish
Pages (from-to)275-278
Number of pages4
JournalJournal of Parenteral and Enteral Nutrition
Volume14
Issue number3
DOIs
StatePublished - 1990
Externally publishedYes

Fingerprint

phenytoin
enteral feeding
Phenytoin
Enteral Nutrition
dialysis
Dialysis
Suspensions
Small Intestine
Stomach
Buffers
stomach
buffers
protein aggregates
Membranes
administered dose
Parenteral Nutrition
parenteral feeding
Proteins

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Food Science

Cite this

Effect of pH on the Equilibrium Dialysis of Phenytoin Suspension with and without Enteral Feeding Formula. / Splinter, Michele Y.; Seifert, Charles F.; Bradberry, J. Chris; Allen, Loyd V.

In: Journal of Parenteral and Enteral Nutrition, Vol. 14, No. 3, 1990, p. 275-278.

Research output: Contribution to journalArticle

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abstract = "Significant decreases have been reported in phenytoin absorption when the suspension is combined with continuous enteral feedings. Several theories for this interaction have been proposed including binding of phenytoin to the protein constituents of the enteral formula, phenytoin binding to the calcium in the enteral formula, and inadequate dissolution of the suspension when delivered with the enteral formula due to the high pKa of phenytoin and the acidic nature of the enteral formula. We therefore evaluated the effects of pH levels 2.0, 3.5, 6.0, and 8.0 on the interaction of phenytoin suspension with enteral formula (Osmolite) with equilibrium dialysis using a Spectra/Por 1 (MWCO 6000-8000) molecularporous dialysis membrane. Phenytoin concentrations in the dialysis membrane (internal phase) mimicked the expected stomach concentrations of a 100-mg dose administered in an adult stomach containing 200 ml of gastric fluid. External phase buffers were sampled at 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, and 24.0 hr after the start of the dialysis. The phenytoin concentrations in the external phase were compared between buffer alone or buffer combined with enteral formula at the same pH and time intervals. With pH 2.0 and 3.5 the enteral formula formed an aggregate with suspension whereas no aggregate was formed with pH 6.0 and 8.0. The phenytoin concentrations with pH 2.0 were 26{\%} to 44{\%} lower and with pH 3.5 were 11.5 to 27{\%} lower when phenytoin suspension was combined with enteral solution. However, at 24 hr there was no difference between the two conditions with both pH 2.0 and 3.5. With pH 6.0 there was a significant difference at 24 hr and with pH 8.0 significant differences were reached only at 0.5, 1.0 and 2.0 hr. These results show that the phenytoin suspension/enteral formula interaction is pH dependent. There appears to be a physical entrapment of the large suspension particles when the protein in the enteral solution denatures at lower pH's. These results may in part explain the decreased erratic absorption when phenytoin suspension is combined with enteral feedings. (Journal of Parenteral and Enteral Nutrition 14:275-278, 1990).",
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AU - Allen, Loyd V.

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N2 - Significant decreases have been reported in phenytoin absorption when the suspension is combined with continuous enteral feedings. Several theories for this interaction have been proposed including binding of phenytoin to the protein constituents of the enteral formula, phenytoin binding to the calcium in the enteral formula, and inadequate dissolution of the suspension when delivered with the enteral formula due to the high pKa of phenytoin and the acidic nature of the enteral formula. We therefore evaluated the effects of pH levels 2.0, 3.5, 6.0, and 8.0 on the interaction of phenytoin suspension with enteral formula (Osmolite) with equilibrium dialysis using a Spectra/Por 1 (MWCO 6000-8000) molecularporous dialysis membrane. Phenytoin concentrations in the dialysis membrane (internal phase) mimicked the expected stomach concentrations of a 100-mg dose administered in an adult stomach containing 200 ml of gastric fluid. External phase buffers were sampled at 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, and 24.0 hr after the start of the dialysis. The phenytoin concentrations in the external phase were compared between buffer alone or buffer combined with enteral formula at the same pH and time intervals. With pH 2.0 and 3.5 the enteral formula formed an aggregate with suspension whereas no aggregate was formed with pH 6.0 and 8.0. The phenytoin concentrations with pH 2.0 were 26% to 44% lower and with pH 3.5 were 11.5 to 27% lower when phenytoin suspension was combined with enteral solution. However, at 24 hr there was no difference between the two conditions with both pH 2.0 and 3.5. With pH 6.0 there was a significant difference at 24 hr and with pH 8.0 significant differences were reached only at 0.5, 1.0 and 2.0 hr. These results show that the phenytoin suspension/enteral formula interaction is pH dependent. There appears to be a physical entrapment of the large suspension particles when the protein in the enteral solution denatures at lower pH's. These results may in part explain the decreased erratic absorption when phenytoin suspension is combined with enteral feedings. (Journal of Parenteral and Enteral Nutrition 14:275-278, 1990).

AB - Significant decreases have been reported in phenytoin absorption when the suspension is combined with continuous enteral feedings. Several theories for this interaction have been proposed including binding of phenytoin to the protein constituents of the enteral formula, phenytoin binding to the calcium in the enteral formula, and inadequate dissolution of the suspension when delivered with the enteral formula due to the high pKa of phenytoin and the acidic nature of the enteral formula. We therefore evaluated the effects of pH levels 2.0, 3.5, 6.0, and 8.0 on the interaction of phenytoin suspension with enteral formula (Osmolite) with equilibrium dialysis using a Spectra/Por 1 (MWCO 6000-8000) molecularporous dialysis membrane. Phenytoin concentrations in the dialysis membrane (internal phase) mimicked the expected stomach concentrations of a 100-mg dose administered in an adult stomach containing 200 ml of gastric fluid. External phase buffers were sampled at 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, and 24.0 hr after the start of the dialysis. The phenytoin concentrations in the external phase were compared between buffer alone or buffer combined with enteral formula at the same pH and time intervals. With pH 2.0 and 3.5 the enteral formula formed an aggregate with suspension whereas no aggregate was formed with pH 6.0 and 8.0. The phenytoin concentrations with pH 2.0 were 26% to 44% lower and with pH 3.5 were 11.5 to 27% lower when phenytoin suspension was combined with enteral solution. However, at 24 hr there was no difference between the two conditions with both pH 2.0 and 3.5. With pH 6.0 there was a significant difference at 24 hr and with pH 8.0 significant differences were reached only at 0.5, 1.0 and 2.0 hr. These results show that the phenytoin suspension/enteral formula interaction is pH dependent. There appears to be a physical entrapment of the large suspension particles when the protein in the enteral solution denatures at lower pH's. These results may in part explain the decreased erratic absorption when phenytoin suspension is combined with enteral feedings. (Journal of Parenteral and Enteral Nutrition 14:275-278, 1990).

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