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No Effect of Digoxin on Rosuvastatin Pharmacokinetics in Healthy Subjects: Utility of Oita Combination for Clinical Drug-Drug Interaction Study.
Clin Transl Sci. 2019 09; 12(5):513-518.CT

Abstract

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/OATP1B3) probe cocktail (Oita combination) for drug-drug interaction (DDI) studies by demonstrating lack of DDI of digoxin on the pharmacokinetics (PKs) 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 (AUClast) after rosuvastatin administration combined with digoxin to that after rosuvastatin administration alone and its 90% confidence interval (CI). As the GMR of AUClast 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.

Authors+Show Affiliations

Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan. Clinical Pharmacology Center, Oita University Hospital, Oita, Japan. General Clinical Research Center, Oita University Hospital, Oita, Japan.Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan.Clinical Pharmacology Center, Oita University Hospital, Oita, Japan. Department of Medical Ethics, Faculty of Medicine, Oita University, Oita, Japan.General Clinical Research Center, Oita University Hospital, Oita, Japan.Shinagawa Research and Development Center, Sato Pharmaceutical Co., Ltd., Tokyo, Japan.Shinagawa Research and Development Center, Sato Pharmaceutical Co., Ltd., Tokyo, Japan.Clinical Research Department, Sato Pharmaceutical Co., Ltd., Tokyo, Japan.Research and Development, Seren Pharmaceuticals Inc., Tokyo, Japan.Research and Development, Seren Pharmaceuticals Inc., Tokyo, Japan.Biostatistics Center, Kurume University, Fukuoka, Japan.Department of Research, Clinical Trial Center, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Oita, Japan. Clinical Pharmacology Center, Oita University Hospital, Oita, Japan. General Clinical Research Center, Oita University Hospital, Oita, Japan.

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31095880

Citation

Otani, Naoyuki, et al. "No Effect of Digoxin On Rosuvastatin Pharmacokinetics in Healthy Subjects: Utility of Oita Combination for Clinical Drug-Drug Interaction Study." Clinical and Translational Science, vol. 12, no. 5, 2019, pp. 513-518.
Otani N, Wakuda H, Imai H, et al. No Effect of Digoxin on Rosuvastatin Pharmacokinetics in Healthy Subjects: Utility of Oita Combination for Clinical Drug-Drug Interaction Study. Clin Transl Sci. 2019;12(5):513-518.
Otani, N., Wakuda, H., Imai, H., Kuranari, M., Ishii, Y., Ito, Y., Okubo, A., Ogawa, O., Takeda, K., Ohyama, T., Hasunuma, T., & Uemura, N. (2019). No Effect of Digoxin on Rosuvastatin Pharmacokinetics in Healthy Subjects: Utility of Oita Combination for Clinical Drug-Drug Interaction Study. Clinical and Translational Science, 12(5), 513-518. https://doi.org/10.1111/cts.12646
Otani N, et al. No Effect of Digoxin On Rosuvastatin Pharmacokinetics in Healthy Subjects: Utility of Oita Combination for Clinical Drug-Drug Interaction Study. Clin Transl Sci. 2019;12(5):513-518. PubMed PMID: 31095880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - No Effect of Digoxin on Rosuvastatin Pharmacokinetics in Healthy Subjects: Utility of Oita Combination for Clinical Drug-Drug Interaction Study. AU - Otani,Naoyuki, AU - Wakuda,Hirokazu, AU - Imai,Hiromitsu, AU - Kuranari,Masae, AU - Ishii,Yasuyuki, AU - Ito,Yuko, AU - Okubo,Akihiro, AU - Ogawa,Osamu, AU - Takeda,Kenji, AU - Ohyama,Tetsuji, AU - Hasunuma,Tomoko, AU - Uemura,Naoto, Y1 - 2019/06/04/ PY - 2019/02/22/received PY - 2019/04/11/accepted PY - 2019/5/17/pubmed PY - 2020/8/20/medline PY - 2019/5/17/entrez SP - 513 EP - 518 JF - Clinical and translational science JO - Clin Transl Sci VL - 12 IS - 5 N2 - 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/OATP1B3) probe cocktail (Oita combination) for drug-drug interaction (DDI) studies by demonstrating lack of DDI of digoxin on the pharmacokinetics (PKs) 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 (AUClast) after rosuvastatin administration combined with digoxin to that after rosuvastatin administration alone and its 90% confidence interval (CI). As the GMR of AUClast 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. SN - 1752-8062 UR - https://www.unboundmedicine.com/medline/citation/31095880/No_Effect_of_Digoxin_on_Rosuvastatin_Pharmacokinetics_in_Healthy_Subjects:_Utility_of_Oita_Combination_for_Clinical_Drug_Drug_Interaction_Study_ L2 - https://doi.org/10.1111/cts.12646 DB - PRIME DP - Unbound Medicine ER -