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 x 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 (AUC t) geometric least-squares mean ratio (GMR) -AUC t GMR, 89.7; 90% confidence interval (CI), 81.0-99.4 for metformin; AUC t GMR, 96.2; 90% CI, 86.3-107.1 for losartan; and AUC t GMR, 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 (C-max, (ss)) -C-max, (ss) GMR, 87.3; 90% CI, 76.2-100.0 for metformin; C-max,C- ss GMR, 90.5; 90% CI, 78.3-104.6 for losartan; and C-max,C- ss GMR, 81.4; 90% CI, 69.5-95.3 for linagliptin. Coadministration of DW1029M with metformin, losartan, or linagliptin was well tolerated.