Jun 1, 1976

The absorption of warfarin from the rat small intestine in situ

The Journal of Pharmacy and Pharmacology
R J Julkunen

Abstract

The in situ absorption from the rat small intestine of the weakly acidic drug, warfarin (pKa 5-05), at 200 mug ml-1 in the instilled fluid with initial pH levels of 3, 5, 7 or 8 has been examined. These initial pH's in the buffer changed rapidly towards neutrality. The buffers at pH's 3 and 5 probably caused different amounts of warfarin precipitation, which resulted in different rates of warfarin disappearance from the instilled fluid which paralleled the initial rates of accumulation of warfarin in (or on) the intestinal wall. Where greater drug precipitation had probably occurred the initial rates of absorption into the plasma were slower. At the initial pH of 3 and by solubilization of warfarin with propylene glycol, the rate of absorption was similar to that from a fluid of pH 7. Propylene glycol in 15% solution did not affect the system significantly. The relatively high transfer of warfarin into octanol from buffer solution at pH 7 might indicate that the small fraction of unionized drug (1 : 100) at pH 7 is enough for remarkable transfer of this highly lipid-soluble drug.

  • References4
  • Citations2

References

  • References4
  • Citations2

Mentioned in this Paper

Buffers
ATP8A2 gene
IL17F gene
Propylene Glycol
Warfarin
Soluble
Propylene Glycols
ATP8A2 wt Allele
Octanols
Acids

About this Paper

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