title: Phase 1 and Pharmacokinetic Drug-Drug Interaction Study of Metformin, Losartan, and Linagliptin Coadministered With DW1029M in Healthy Volunteers.
abstract: We investigated botanical drug-pharmaceutical drug interactions between DW1029M (a botanical extract of Morus alba linne root bark and Puerariae radix) and metformin, losartan, and linagliptin in the steady state. Three studies were conducted as randomized, open-label, 2-period, 2-treatment, multiple-dose, 2-way crossover designs. Eligible subjects received metformin (500 mg twice daily), losartan (50 mg once daily), or linagliptin (5 mg once daily) with DW1029M (300 mg × 2T twice daily) every 12 hours on days 1 through 6 and a single dose on the morning of day 7. Coadministration of DW1029M with metformin, losartan, or linagliptin had no clinically relevant effects based on the area under the plasma concentration-time curve (AUCτ) geometric least-squares mean ratio (GMR) - AUCτGMR, 89.7; 90% confidence interval (CI), 81.0-99.4 for metformin; AUCτGMR, 96.2; 90%CI, 86.3-107.1 for losartan; and AUCτGMR, 89.7; 90%CI, 83.2-96.6 for linagliptin. In addition, coadministration of DW1029M did not have any clinically meaningful effect on the maximum plasma concentration (Cmax,ss) - Cmax,ssGMR, 87.3; 90%CI, 76.2-100.0 for metformin; Cmax,ssGMR, 90.5; 90%CI, 78.3-104.6 for losartan; and Cmax,ssGMR, 81.4; 90%CI, 69.5-95.3 for linagliptin. Coadministration of DW1029M with metformin, losartan, or linagliptin was well tolerated.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital and College of Medicine, Seoul, Republic of Korea.
authors.forename: Seol Ju
authors.initials: SJ
authors.lastname: Moon
authors.affiliation: Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-ang University, Seoul, Republic of Korea.|Dongwha Pharmaceuticals Project Team, Seoul, Republic of Korea.
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Lim
authors.affiliation: Dongwha Pharmaceuticals Project Team, Seoul, Republic of Korea.
authors.forename: Hwan Bong
authors.initials: HB
authors.lastname: Jang
authors.affiliation: Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.|Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Min-Gul
authors.initials: MG
authors.lastname: Kim
authors.affiliation: Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Jeon
mesh_terms: D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004347:Drug Interactions; D064368:Healthy Volunteers; D006801:Humans; D000069476:Linagliptin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019808:Losartan / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D031625:Morus / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics*; D029908:Pueraria / Q000737:chemistry*; D055815:Young Adult
chemical_list: D010936:Plant Extracts; D000069476:Linagliptin; D008687:Metformin; D019808:Losartan
keywords: DW1029M; botanical drug; diabetic nephropathy; drug interaction; pharmacokinetic