Interaction of pristinamycin IA with P-glycoprotein in human intestinal epithelial cells

Eur J Pharmacol. 1995 Jan 16;288(2):187-92. doi: 10.1016/0922-4106(95)90193-0.


Pristinamycin IA is a cyclo-peptidic macrolactone antibiotic belonging to the streptogramin family. In the present work, the interaction of pristinamycin IA with the multidrug transporter P-glycoprotein was investigated in the differentiated human intestinal epithelial cell line Caco-2. Pristinamycin IA specifically inhibited the efflux of the P-glycoprotein substrate [3H]vinblastine, thus increasing the cellular accumulation of the drug. Pristinamycin IA also reduced by 70% the basolateral to apical secretion of [3H]vinblastine across Caco-2 cell monolayers. The cellular accumulation of [14C]pristinamycin IA was very low and was increased by P-glycoprotein inhibitors (verapamil, chlorpromazine and reserpine). The basolateral to apical transport of [14C]pristinamycin IA was 100-fold higher than apical to basolateral passage. This polarized transport was inhibited by verapamil and by ATP depletion. The results suggest that pristinamycin IA is a substrate for the P-glycoprotein, a finding which may have important consequences for the pharmacokinetics of this drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Cell Line
  • Chlorpromazine / pharmacology
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Reserpine / pharmacology
  • Verapamil / pharmacology
  • Vinblastine / metabolism
  • Virginiamycin / pharmacology*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Virginiamycin
  • Vinblastine
  • Reserpine
  • Verapamil
  • Chlorpromazine