Dialysis of the rectum for sampling drug concentrations in the luminal extracellular fluid of the gut: technique and precision

Aliment Pharmacol Ther. 1998 Jul;12(7):679-84. doi: 10.1046/j.1365-2036.1998.00352.x.

Abstract

Background: It is useful to measure the luminal concentration of drugs which act in the gut. Dialysis of the rectum has not previously been used or validated for this purpose.

Aim: To determine the precision of rectal dialysis for measuring rectal drug concentrations.

Methods: To establish the duration of dialysis required to approach equilibrium, the rate of methotrexate diffusion into dialysis bags was first determined in vitro. The precision of rectal dialysis for sampling the methotrexate concentration of colonic lumen extracellular fluid was determined in seven subjects who underwent two consecutive dialysis procedures. Subjects treated with subcutaneous methotrexate for refractory inflammatory bowel disease were studied.

Results: Methotrexate crossed the dialysis membrane by a first-order process, and after a 2 h in vitro dialysis, equilibration was 74 +/- 2% (mean +/- s.d.) complete. Rectal dialysis was well tolerated by all subjects. The mean +/- s.e. methotrexate concentration of 3.6 +/- 1.1 nmol/L in the first dialysate was not significantly different from 3.6 +/- 0.9 nmol/L in the second dialysate. P = 0.99 (paired two-tailed t-test). Similar precision was obtained for an endogenous molecule, potassium, secreted by the rectal mucosa.

Conclusions: Dialysis of the rectum is a well tolerated and precise technique for sampling the colonic lumen extracellular fluid for quantitative analyses of exogenous and endogenous substances.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antirheumatic Agents / analysis*
  • Antirheumatic Agents / pharmacokinetics
  • Antirheumatic Agents / therapeutic use
  • Dialysis / instrumentation
  • Dialysis / methods*
  • Half-Life
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / metabolism
  • Linear Models
  • Male
  • Methotrexate / analysis*
  • Methotrexate / pharmacokinetics
  • Methotrexate / therapeutic use
  • Rectum / chemistry*

Substances

  • Antirheumatic Agents
  • Methotrexate