Pitavastatin is a more sensitive and selective organic anion-transporting polypeptide 1B clinical probe than rosuvastatin

Br J Clin Pharmacol. 2014 Sep;78(3):587-98. doi: 10.1111/bcp.12377.


Aims: Rosuvastatin and pitavastatin have been proposed as probe substrates for the organic anion-transporting polypeptide (OATP) 1B, but clinical data on their relative sensitivity and selectivity to OATP1B inhibitors are lacking. A clinical study was therefore conducted to determine their relative suitability as OATP1B probes using single oral (PO) and intravenous (IV) doses of the OATP1B inhibitor rifampicin, accompanied by a comprehensive in vitro assessment of rifampicin inhibitory potential on statin transporters.

Methods: The clinical study comprised of two separate panels of eight healthy subjects. In each panel, subjects were randomized to receive a single oral dose of rosuvastatin (5 mg) or pitavastatin (1 mg) administered alone, concomitantly with rifampicin (600 mg) PO or IV. The in vitro transporter studies were performed using hepatocytes and recombinant expression systems.

Results: Rifampicin markedly increased exposures of both statins, with greater differential increases after PO vs. IV rifampicin only for rosuvastatin. The magnitudes of the increases in area under the plasma concentration-time curve were 5.7- and 7.6-fold for pitavastatin and 4.4- and 3.3-fold for rosuvastatin, after PO and IV rifampicin, respectively. In vitro studies showed that rifampicin was an inhibitor of OATP1B1 and OATP1B3, breast cancer resistance protein and multidrug resistance protein 2, but not of organic anion transporter 3.

Conclusions: The results indicate that pitavastatin is a more sensitive and selective and thus preferred clinical OATP1B probe substrate than rosuvastatin, and that a single IV dose of rifampicin is a more selective OATP1B inhibitor than a PO dose.

Keywords: breast cancer resistance protein; drug-drug interactions; organic anion-transporting polypeptide 1B; pitavastatin; regulatory guidance; rosuvastatin.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Adult
  • Area Under Curve
  • Cross-Over Studies
  • Drug Interactions
  • Female
  • Fluorobenzenes / pharmacokinetics*
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
  • Liver-Specific Organic Anion Transporter 1
  • Male
  • Middle Aged
  • Organic Anion Transporters / antagonists & inhibitors
  • Organic Anion Transporters / metabolism
  • Organic Anion Transporters, Sodium-Independent / antagonists & inhibitors
  • Organic Anion Transporters, Sodium-Independent / metabolism
  • Pyrimidines / pharmacokinetics*
  • Quinolines / pharmacokinetics*
  • Rifampin / administration & dosage
  • Rifampin / pharmacology*
  • Rosuvastatin Calcium
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Sulfonamides / pharmacokinetics*
  • Young Adult


  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • Organic Anion Transporters, Sodium-Independent
  • Pyrimidines
  • Quinolines
  • SLCO1B1 protein, human
  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Sulfonamides
  • Rosuvastatin Calcium
  • pitavastatin
  • Rifampin