No evidence for the involvement of the multidrug resistance-associated protein and/or the monocarboxylic acid transporter in the intestinal transport of fluvastatin in the rat

AAPS PharmSci. 2000;2(3):E26. doi: 10.1208/ps020327.

Abstract

Fluvastatin, an amphiphilic anion, shows a nonlinear increase in effective intestinal permeability (P(eff)) with increasing lumenal concentrations in rats. The main objective of this study was to investigate whether or not this observation could be attributed to an efflux-mediated transport by the multidrug resistance-associated protein (MRP). In parallel, we investigated the possible involvement of the monocarboxylic acid transporter (MCT) in the rapid intestinal absorption of fluvastatin. Single-pass perfusions were performed in the ileum and colon of the rat, with and without the presence of well-established inhibitors/substrates for the MRP (probenecid) and the MCT (nicotinic acid). The results suggest that neither the MRP nor the MCT are involved to any significant extent in the absorption process of fluvastatin in the rat intestine. Thus, the previously reported concentration-dependent P(eff) of fluvastatin in these intestinal regions of the rat is probably not attributable to saturation of any efflux mediated by MRP.

MeSH terms

  • Acyl Coenzyme A / antagonists & inhibitors*
  • Animals
  • Colon / metabolism
  • Enzyme Inhibitors / metabolism*
  • Fatty Acids, Monounsaturated / metabolism*
  • Fluvastatin
  • Ileum / metabolism
  • Indoles / metabolism*
  • Intestinal Absorption
  • Intestinal Mucosa / metabolism*
  • Male
  • Membrane Transport Proteins*
  • Monocarboxylic Acid Transporters / metabolism*
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Niacin / pharmacology
  • Probenecid / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Acyl Coenzyme A
  • Enzyme Inhibitors
  • Fatty Acids, Monounsaturated
  • Indoles
  • Membrane Transport Proteins
  • Monocarboxylic Acid Transporters
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • 3-hydroxy-3-methylglutaryl-coenzyme A
  • Niacin
  • Fluvastatin
  • Probenecid
  • multidrug resistance-associated protein 1