Drug transport V: Mechanism of potassium‐ion inhibition of passive transfer of solutes across everted rat intestine

Michael Mayersohn, Milo Gibaldi, Barbara Grundhofer

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

In previous reports, it was shown that the inclusion of certain cations and sugars in the drug–buffer solution, or other alteration in the basic buffer solution, that results in net tissue fluid uptake also produces a marked reduction of passive solute transfer across the everted rat intestine. Since the extent of inhibition of intestinal transfer under any given condition varied considerably from one drug to another, it was decided to examine the effect of potassium ion (K+), a particularly pronounced inhibitor, on the intestinal transfer of a series of solute molecules of widely different permeability characteristics. The quantitative replacement of Na+ by K+ in a Krebs bicarbonate buffer resulted in some degree of transfer inhibition of every compound studied. An inverse relationship was found between the degree of transfer inhibition and permeability. The intestinal transfer of poorly permeable compounds such as bromthymol blue or eosine blue was virtually abolished in the presence of K+. A high degree of correlation was noted between percent inhibition and molecular weight of solute molecules, suggesting that the most important parameter influencing the extent of inhibition of transfer is the molecular size of the compound. A mechanism is proposed whereby polar compounds are assumed to traverse the isolated, everted rat intestine via intercellular channels existing between adjacent mucosal epithelium cells. When the intestine is exposed to buffer solutions causing tissue fluid uptake, a portion of the fluid penetrates the mucosal cell, causing swelling of the cell and producing a narrowing of the apical portion of the intercellular channel.

Original languageEnglish (US)
Pages (from-to)1813-1817
Number of pages5
JournalJournal of pharmaceutical sciences
Volume60
Issue number12
DOIs
StatePublished - Dec 1971

Keywords

  • Drug transport, everted rat intestine—potassiumion inhibition
  • Potassium ion—mechanism of passive‐transport inhibition
  • Tissue fluid uptake relationship—drug transport

ASJC Scopus subject areas

  • Pharmaceutical Science

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