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Intestinal permeability of mitragynine in rats using in situ absorption model

J D Yuvenesan Jagabalan1, Vikneswaran Murugaiyah2, Hadzliana Zainal2

  • 1a Centre for Drug Research , Universiti Sains Malaysia , Penang 11800 , Malaysia.

Journal of Asian Natural Products Research
|April 19, 2018
PubMed

Insights

Mitragynine shows high intestinal permeability, readily crossing the gut barrier. Its absorption is unaffected by common drug transporters like P-glycoprotein and CYP3A4 inhibitors.

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Gastrointestinal Physiology

Background:

  • Understanding drug absorption is crucial for effective dosing.
  • Mitragynine, a key alkaloid in kratom, has shown potential therapeutic effects but its pharmacokinetic properties require detailed investigation.
  • Intestinal permeability influences oral bioavailability and drug efficacy.

Purpose of the Study:

  • To investigate the in situ intestinal permeability of mitragynine.
  • To determine the influence of P-glycoprotein (P-gp) and Cytochrome P450 3A4 (CYP3A4) on mitragynine's intestinal absorption.

Main Methods:

  • Utilized a single-pass intestinal perfusion (SPIP) model in rat small intestine.
  • Assessed mitragynine permeability in the absence and presence of P-gp and CYP3A4 inhibitors (azithromycin and ciprofloxacin).
  • Quantified effective permeability (Peff) values for mitragynine.

Main Results:

  • Mitragynine exhibited high intestinal permeability, with an effective permeability (Peff) of 1.11 × 10⁻⁴ cm/s.
  • This permeability is comparable to highly permeable drugs like propranolol.
  • Neither P-gp inhibitors (azithromycin) nor CYP3A4 inhibitors (ciprofloxacin), alone or in combination, altered mitragynine's intestinal permeability.

Conclusions:

  • Mitragynine is readily absorbed across the intestinal epithelium due to its high intrinsic permeability.
  • Mitragynine's intestinal transport is not significantly mediated or affected by P-glycoprotein or CYP3A4.
  • These findings suggest a straightforward absorption mechanism for mitragynine, independent of these major efflux and metabolic pathways.
Keywords:
CYP3A4MitragynineP-glycoproteinbiopharmaceutic classification systempermeability

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