J Huguet1,2, J Lu1, F Gaudette1, J-L Chiasson1,3,4, P Hamet1,3,4, V Michaud1,2,4, J Turgeon5,6,7,8,9. 1. CRCHUM, Centre de recherche du Centre hospitalier de l'Université de de Montréal, 900 Saint-Denis Street, Montréal, Quebec, H2X 0A9, Canada. 2. Faculty of Pharmacy, University of Montreal, 2940, chemin de la Polytechnique, Montreal, Quebec, H3T 1J4, Canada. 3. Faculty of Medicine, University of Montreal, 2900, boulevard Édouard-Montpetit, Montreal, Quebec, H3T 1J4, Canada. 4. Research Group on Diabetes and Metabolic Regulation, CRCHUM, 900 Saint-Denis Street, Montreal, Quebec, H2X 0A9, Canada. 5. 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. 6. Faculty of Pharmacy, University of Montreal, 2940, chemin de la Polytechnique, Montreal, Quebec, H3T 1J4, Canada. jturgeon@tabularasahealthcare.com. 7. Faculty of Medicine, University of Montreal, 2900, boulevard Édouard-Montpetit, Montreal, Quebec, H3T 1J4, Canada. jturgeon@tabularasahealthcare.com. 8. Research Group on Diabetes and Metabolic Regulation, CRCHUM, 900 Saint-Denis Street, Montreal, Quebec, H2X 0A9, Canada. jturgeon@tabularasahealthcare.com. 9. Tabula Rasa Healthcare, 228 Strawbridge, Room 112, Moorestown, NJ, 08057, USA. jturgeon@tabularasahealthcare.com.
Abstract
PURPOSE: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 asingle 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.
RCT Entities:
PURPOSE: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.
Entities:
Keywords:
ABCG2; BCRP; Drug interaction; Pantoprazole; Pharmacokinetics; Rosuvastatin; Transporters
Authors: Manthena V Varma; Charles J Rotter; Jonathan Chupka; Kevin M Whalen; David B Duignan; Bo Feng; John Litchfield; Theunis C Goosen; Ayman F El-Kattan Journal: Mol Pharm Date: 2011-07-11 Impact factor: 4.939
Authors: B Tomlinson; M Hu; V W Y Lee; S S H Lui; T T W Chu; E W M Poon; G T C Ko; L Baum; L S Tam; E K Li Journal: Clin Pharmacol Ther Date: 2010-02-03 Impact factor: 6.875
Authors: Dennis W Schneck; Bruce K Birmingham; Julie A Zalikowski; Patrick D Mitchell; Yi Wang; Paul D Martin; Kenneth C Lasseter; Colin D A Brown; Amy S Windass; Ali Raza Journal: Clin Pharmacol Ther Date: 2004-05 Impact factor: 6.875
Authors: Paul D Martin; Mike J Warwick; Aaron L Dane; Steve J Hill; Petrina B Giles; Paul J Phillips; Eva Lenz Journal: Clin Ther Date: 2003-11 Impact factor: 3.393