Human jejunal permeability of cyclosporin A: Influence of surfactants on P-glycoprotein efflux in Caco-2 cells

Yu Yuan Chiu, Kazutaka Higaki, Brien L. Neudeck, Jeffrey L. Barnett, Lynda S. Welage, Gordon L. Amidon

Research output: Contribution to journalArticlepeer-review

105 Citations (Scopus)


Purpose. The purpose of this work was to determine the jejunal permeability of cyclosporin A (CsA) in humans and whether formulation variables modulate the effects of P-glycoprotein (P-gp) on the permeability of CsA in Caco-2 cells. Methods. A solution containing CsA, phenylalanine, propranolol, polyethyleneglycol (PEG) 400, and PEG 4000 was perfused through a 10-cm jejunal segment in 12 subjects. Caco-2 transport studies were performed using previously reported methodology. Results. The mean Peff (±SD) of CsA in humans was 1.65 (0.53). The mean permeabilities for phenylalanine, propranolol, and PEG 400 were 4.54 (2.39), 2.90 (1.28), and 0.83 (0.51) × 10-4 cm/s, respectively. The presence of surfactants significantly decreased the permeabilities of CsA in both directions in Caco-2 cells. Conclusions. The results suggest that the effects of surfactants via micellar solubilization and inhibition of P-gp efflux on CsA transport in Caco-2 cells are significant. CsA can rightly be classified as a low solubility-high permeability Class II BCS drug and its highly variable absorption from Sandimmune® oral formulations is the result of poor dissolution characteristics.

Original languageEnglish
Pages (from-to)749-756
Number of pages8
JournalPharmaceutical research
Issue number5
Publication statusPublished - May 1 2003


  • Biopharmaceutic classification system
  • Caco-2 cell culture
  • Cyclosporin A
  • Intestinal permeability
  • P-glycoprotein

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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