title: Interaction of pristinamycin IA with P-glycoprotein in human intestinal epithelial cells.
abstract: 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.
authors.affiliation: UMR133 CNRS/RPR, Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France.
authors.forename: V
authors.initials: V
authors.lastname: Phung-Ba
authors.forename: A
authors.initials: A
authors.lastname: Warnery
authors.forename: D
authors.initials: D
authors.lastname: Scherman
authors.forename: P
authors.initials: P
authors.lastname: Wils
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D002460:Cell Line; D002746:Chlorpromazine / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D014747:Vinblastine / Q000378:metabolism; D014769:Virginiamycin / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014769:Virginiamycin; D014747:Vinblastine; D012110:Reserpine; D014700:Verapamil; D002746:Chlorpromazine