Open AccessNo Effect of Digoxin on Rosuvastatin Pharmacokinetics in Healthy Subjects: Utility of Oita Combination for Clinical Drug–Drug Interaction Study
Author(s) -
Otani Naoyuki,
Wakuda Hirokazu,
Imai Hiromitsu,
Kuranari Masae,
Ishii Yasuyuki,
Ito Yuko,
Okubo Akihiro,
Ogawa Osamu,
Takeda Kenji,
Ohyama Tetsuji,
Hasunuma Tomoko,
Uemura Naoto
Publication year - 2019
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12646
Subject(s) - rosuvastatin , digoxin , pharmacokinetics , medicine , rosuvastatin calcium , pharmacology , drug interaction , area under the curve , organic anion transporting polypeptide , drug , transporter , chemistry , heart failure , biochemistry , gene
This study evaluated the utility of combination of digoxin (0.25 mg) and rosuvastatin (5 mg) as a new transporter (P‐glycoprotein/breast cancer resistance protein/organic anion‐transporting polypeptide ( OATP )1B1/ OATP 1B3) probe cocktail (Oita combination) for drug–drug interaction ( DDI ) studies by demonstrating lack of DDI of digoxin on the pharmacokinetics ( PK s) of rosuvastatin, as it was already known that rosuvastatin did not affect digoxin PK . This was an open‐label, two‐period study in which the primary end points were the geometric mean ratio ( GMR ) of the area under the plasma rosuvastatin concentration‐time curve from time zero to last ( AUC last ) after rosuvastatin administration combined with digoxin to that after rosuvastatin administration alone and its 90% confidence interval ( CI ). As the GMR of AUC last was 0.974 and its 90% CI was 0.911–1.042, it was judged that digoxin does not affect rosuvastatin PK . Results of this study have rationalized utility of the Oita combination as a transporter probe cocktail for clinical DDI studies.