title: No effects of pantoprazole on the pharmacokinetics of rosuvastatin in healthy subjects.
abstract: OBJECTIVE
  Rosuvastatin disposition is modulated by the expression and activity of several membrane transporters including BCRP (ABCG2). The objective of our study was to investigate the effects of pantoprazole, a previously proposed BCRP inhibitor, on the disposition of rosuvastatin.
  
  
  METHODS
  The impact of pantoprazole (40 mg ID for 2 days) on rosuvastatin pharmacokinetics was evaluated in healthy volunteers (n = 16) who received a single oral dose of rosuvastatin (10 mg) either alone or with pantoprazole. Rosuvastatin, N-desmethylrosuvastatin, and rosuvastatin lactone levels were quantified in plasma while rosuvastatin and N-desmethylrosuvastatin excretion were measured in urine.
  
  
  RESULTS
  Ratios and 90 % standard confidence interval of geometric means for C max (1.03 [0.91-1.16]), AUC0-∞ (1.03 [0.89-1.19]) and renal clearance (0.96 [0.85-1.09]) were all within the pre-specified range of 0.8-1.25, indicating a lack of drug-drug interaction between pantoprazole and rosuvastatin.
  
  
  CONCLUSIONS
  Concomitant administration of pantoprazole with rosuvastatin did not affect rosuvastatin plasma concentrations. The use of pantoprazole as a BCRP inhibitor should be revisited when characterizing BCRP-mediated transport in humans.
authors.affiliation: CRCHUM, Centre de recherche du Centre hospitalier de l'Université de de Montréal, 900 Saint-Denis Street, Montréal, Quebec, H2X 0A9, Canada.|Faculty of Pharmacy, University of Montreal, 2940, chemin de la Polytechnique, Montreal, Quebec, H3T 1J4, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Huguet
authors.affiliation: CRCHUM, Centre de recherche du Centre hospitalier de l'Université de de Montréal, 900 Saint-Denis Street, Montréal, Quebec, H2X 0A9, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.affiliation: CRCHUM, Centre de recherche du Centre hospitalier de l'Université de de Montréal, 900 Saint-Denis Street, Montréal, Quebec, H2X 0A9, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Gaudette
authors.affiliation: CRCHUM, Centre de recherche du Centre hospitalier de l'Université de de Montréal, 900 Saint-Denis Street, Montréal, Quebec, H2X 0A9, Canada.|Faculty of Medicine, University of Montreal, 2900, boulevard Édouard-Montpetit, Montreal, Quebec, H3T 1J4, Canada.|Research Group on Diabetes and Metabolic Regulation, CRCHUM, 900 Saint-Denis Street, Montreal, Quebec, H2X 0A9, Canada.
authors.forename: J-L
authors.initials: JL
authors.lastname: Chiasson
authors.affiliation: CRCHUM, Centre de recherche du Centre hospitalier de l'Université de de Montréal, 900 Saint-Denis Street, Montréal, Quebec, H2X 0A9, Canada.|Faculty of Medicine, University of Montreal, 2900, boulevard Édouard-Montpetit, Montreal, Quebec, H3T 1J4, Canada.|Research Group on Diabetes and Metabolic Regulation, CRCHUM, 900 Saint-Denis Street, Montreal, Quebec, H2X 0A9, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Hamet
authors.affiliation: CRCHUM, Centre de recherche du Centre hospitalier de l'Université de de Montréal, 900 Saint-Denis Street, Montréal, Quebec, H2X 0A9, Canada.|Faculty of Pharmacy, University of Montreal, 2940, chemin de la Polytechnique, Montreal, Quebec, H3T 1J4, Canada.|Research Group on Diabetes and Metabolic Regulation, CRCHUM, 900 Saint-Denis Street, Montreal, Quebec, H2X 0A9, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Michaud
authors.affiliation: CRCHUM, Centre de recherche du Centre hospitalier de l'Université de de Montréal, 900 Saint-Denis Street, Montréal, Quebec, H2X 0A9, Canada. jturgeon@tabularasahealthcare.com.|Faculty of Pharmacy, University of Montreal, 2940, chemin de la Polytechnique, Montreal, Quebec, H3T 1J4, Canada. jturgeon@tabularasahealthcare.com.|Faculty of Medicine, University of Montreal, 2900, boulevard Édouard-Montpetit, Montreal, Quebec, H3T 1J4, Canada. jturgeon@tabularasahealthcare.com.|Research Group on Diabetes and Metabolic Regulation, CRCHUM, 900 Saint-Denis Street, Montreal, Quebec, H2X 0A9, Canada. jturgeon@tabularasahealthcare.com.|Tabula Rasa Healthcare, 228 Strawbridge, Room 112, Moorestown, NJ, 08057, USA. jturgeon@tabularasahealthcare.com.
authors.forename: J
authors.initials: J
authors.lastname: Turgeon
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000037:antagonists & inhibitors / Q000235:genetics; D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D004347:Drug Interactions; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D007783:Lactones / Q000097:blood; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D000077402:Pantoprazole; D020641:Polymorphism, Single Nucleotide; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000097:blood; D000068718:Rosuvastatin Calcium / Q000097:blood / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000097:blood; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007783:Lactones; D027381:Liver-Specific Organic Anion Transporter 1; C551067:N-desmethylrosuvastatin; D009363:Neoplasm Proteins; D054328:Proton Pump Inhibitors; D011743:Pyrimidines; C503999:SLCO1B1 protein, human; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D000077402:Pantoprazole; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; C551068:rosuvastatin lactone
keywords: ABCG2; BCRP; Drug interaction; Pantoprazole; Pharmacokinetics; Rosuvastatin; Transporters