Tags

Type your tag names separated by a space and hit enter

Pharmacokinetic Evaluation of a Drug Transporter Cocktail Consisting of Digoxin, Furosemide, Metformin, and Rosuvastatin.
Clin Pharmacol Ther. 2016 Sep; 100(3):259-67.CP

Abstract

This article reports the clinical investigation of a probe drug cocktail containing substrates of key drug transporters. Single oral doses of 0.25 mg digoxin (P-gp), 5 mg furosemide (OAT1 and OAT3), 500 mg metformin (OCT2, MATE1, and MATE2-K), and 10 mg rosuvastatin (OATP1B1, OATP1B3, and BCRP) were administered separately or as a cocktail in a randomized six-period crossover trial in 24 healthy male volunteers. As a cocktail, relative bioavailabilities of digoxin and metformin and furosemide AUC0-tz were similar to separate dosing. However, when administered as a cocktail the Cmax of furosemide was 19.1% lower and the Cmax and AUC0-tz of rosuvastatin were 38.6% and 43.4% higher, respectively. In addition, the effects of increased doses of metformin or furosemide on the cocktail were investigated in 11 and 12 subjects, respectively. The cocktail explored in this trial has the potential to be used for the in vivo screening of transporter-mediated drug-drug interactions. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Authors+Show Affiliations

Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.Nippon Boehringer Ingelheim, Kobe, Japan.Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, USA.Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

27256812

Citation

Stopfer, P, et al. "Pharmacokinetic Evaluation of a Drug Transporter Cocktail Consisting of Digoxin, Furosemide, Metformin, and Rosuvastatin." Clinical Pharmacology and Therapeutics, vol. 100, no. 3, 2016, pp. 259-67.
Stopfer P, Giessmann T, Hohl K, et al. Pharmacokinetic Evaluation of a Drug Transporter Cocktail Consisting of Digoxin, Furosemide, Metformin, and Rosuvastatin. Clin Pharmacol Ther. 2016;100(3):259-67.
Stopfer, P., Giessmann, T., Hohl, K., Sharma, A., Ishiguro, N., Taub, M. E., Zimdahl-Gelling, H., Gansser, D., Wein, M., Ebner, T., & Müller, F. (2016). Pharmacokinetic Evaluation of a Drug Transporter Cocktail Consisting of Digoxin, Furosemide, Metformin, and Rosuvastatin. Clinical Pharmacology and Therapeutics, 100(3), 259-67. https://doi.org/10.1002/cpt.406
Stopfer P, et al. Pharmacokinetic Evaluation of a Drug Transporter Cocktail Consisting of Digoxin, Furosemide, Metformin, and Rosuvastatin. Clin Pharmacol Ther. 2016;100(3):259-67. PubMed PMID: 27256812.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic Evaluation of a Drug Transporter Cocktail Consisting of Digoxin, Furosemide, Metformin, and Rosuvastatin. AU - Stopfer,P, AU - Giessmann,T, AU - Hohl,K, AU - Sharma,A, AU - Ishiguro,N, AU - Taub,M E, AU - Zimdahl-Gelling,H, AU - Gansser,D, AU - Wein,M, AU - Ebner,T, AU - Müller,F, Y1 - 2016/07/29/ PY - 2016/03/01/received PY - 2016/05/24/revised PY - 2016/05/28/accepted PY - 2016/6/4/entrez PY - 2016/6/4/pubmed PY - 2017/5/16/medline SP - 259 EP - 67 JF - Clinical pharmacology and therapeutics JO - Clin. Pharmacol. Ther. VL - 100 IS - 3 N2 - This article reports the clinical investigation of a probe drug cocktail containing substrates of key drug transporters. Single oral doses of 0.25 mg digoxin (P-gp), 5 mg furosemide (OAT1 and OAT3), 500 mg metformin (OCT2, MATE1, and MATE2-K), and 10 mg rosuvastatin (OATP1B1, OATP1B3, and BCRP) were administered separately or as a cocktail in a randomized six-period crossover trial in 24 healthy male volunteers. As a cocktail, relative bioavailabilities of digoxin and metformin and furosemide AUC0-tz were similar to separate dosing. However, when administered as a cocktail the Cmax of furosemide was 19.1% lower and the Cmax and AUC0-tz of rosuvastatin were 38.6% and 43.4% higher, respectively. In addition, the effects of increased doses of metformin or furosemide on the cocktail were investigated in 11 and 12 subjects, respectively. The cocktail explored in this trial has the potential to be used for the in vivo screening of transporter-mediated drug-drug interactions. © 2016 American Society for Clinical Pharmacology and Therapeutics. SN - 1532-6535 UR - https://www.unboundmedicine.com/medline/citation/27256812/Pharmacokinetic_Evaluation_of_a_Drug_Transporter_Cocktail_Consisting_of_Digoxin_Furosemide_Metformin_and_Rosuvastatin_ L2 - https://doi.org/10.1002/cpt.406 DB - PRIME DP - Unbound Medicine ER -