PMID- 36790596
OWN - NLM
STAT- MEDLINE
DCOM- 20230508
LR  - 20230508
IS  - 1179-187X (Electronic)
IS  - 1175-3277 (Print)
IS  - 1175-3277 (Linking)
VI  - 23
IP  - 3
DP  - 2023 May
TI  - Results From a Randomized, Open-Label, Crossover Study Evaluating the Effect of 
      the Aldosterone Synthase Inhibitor Baxdrostat on the Pharmacokinetics of 
      Metformin in Healthy Human Subjects.
PG  - 277-286
LID - 10.1007/s40256-023-00572-x [doi]
AB  - BACKGROUND: Due to the high comorbidity of diabetes and hypertension, 
      co-administration of metformin with anti-hypertensive drugs is likely. Baxdrostat 
      is an aldosterone synthase inhibitor in development for the potential treatment 
      of hypertension. In vitro data indicated that baxdrostat inhibits the multidrug 
      and toxin extrusion 1 (MATE1) and MATE2-K renal transporters. Metformin is a MATE 
      substrate, so this study assessed potential effects of baxdrostat on the 
      pharmacokinetics of metformin. METHODS: Twenty-seven healthy volunteers received 
      1000 mg metformin alone and 1000 mg metformin in the presence of 10 mg baxdrostat 
      in a randomized, crossover manner. Each treatment was separated by 10 or more 
      days. Blood and urine samples were collected over a 3-day period after each 
      treatment to measure plasma and urine concentrations of metformin. Safety was 
      assessed by adverse events (AEs), physical examinations, electrocardiograms, 
      vital signs, and clinical laboratory evaluations. RESULTS: There were no deaths, 
      serious AEs, discontinuations due to treatment-emergent AEs, or noteworthy 
      increases in AEs with either treatment, indicating that metformin and baxdrostat 
      were well-tolerated when co-administered. Baxdrostat did not significantly affect 
      plasma concentrations or renal clearance of metformin. CONCLUSION: The results of 
      this study suggest that diabetic patients with hypertension receiving both 
      metformin and baxdrostat are unlikely to require dose adjustment. REGISTRATION: 
      ClinicalTrials.gov identifier no. NCT05526690.
CI  - (c) 2023. The Author(s).
FAU - Freeman, Mason W
AU  - Freeman MW
AD  - CinCor Pharma, Inc., Waltham, MA, USA. mfreeman@cincor.com.
FAU - Bond, Mary
AU  - Bond M
AD  - CinRx Pharma, LLC, Cincinnati, OH, USA.
FAU - Murphy, Brian
AU  - Murphy B
AD  - CinRx Pharma, LLC, Cincinnati, OH, USA.
FAU - Hui, James
AU  - Hui J
AD  - CinCor Pharma, Inc., Waltham, MA, USA.
FAU - Isaacsohn, Jonathan
AU  - Isaacsohn J
AD  - CinRx Pharma, LLC, Cincinnati, OH, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT05526690
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20230215
PL  - New Zealand
TA  - Am J Cardiovasc Drugs
JT  - American journal of cardiovascular drugs : drugs, devices, and other 
      interventions
JID - 100967755
RN  - 9100L32L2N (Metformin)
RN  - 0 (Hypoglycemic Agents)
RN  - EC 1.14.15.4 (Cytochrome P-450 CYP11B2)
SB  - IM
MH  - Humans
MH  - *Metformin/pharmacology
MH  - Hypoglycemic Agents/adverse effects/pharmacokinetics
MH  - Cross-Over Studies
MH  - Cytochrome P-450 CYP11B2
MH  - Healthy Volunteers
MH  - Area Under Curve
MH  - *Hypertension/drug therapy
MH  - Drug Interactions
PMC - PMC9930700
COIS- Mason Freeman, MD, is an employee of CinCor Pharma Inc. and receives stock-based 
      compensation. Mary Bond, MS, MBA, is an employee of and has equity in CinRx 
      Pharma, LLC, which has an equity stake in CinCor Pharma Inc. Brian Murphy, MD, 
      MPH, is an employee of and has equity in CinRx Pharma, LLC, which has an equity 
      stake in CinCor Pharma Inc. James Hui, PhD, is an employee of CinCor Pharma Inc. 
      and receives stock-based compensation. Jonathan Isaacson, MD, is an employee of 
      and has equity in CinRx Pharma, LLC, which has an equity stake in CinCor Pharma 
      Inc.
EDAT- 2023/02/16 06:00
MHDA- 2023/05/08 06:43
PMCR- 2023/02/15
CRDT- 2023/02/15 11:20
PHST- 2023/01/19 00:00 [accepted]
PHST- 2023/05/08 06:43 [medline]
PHST- 2023/02/16 06:00 [pubmed]
PHST- 2023/02/15 11:20 [entrez]
PHST- 2023/02/15 00:00 [pmc-release]
AID - 10.1007/s40256-023-00572-x [pii]
AID - 572 [pii]
AID - 10.1007/s40256-023-00572-x [doi]
PST - ppublish
SO  - Am J Cardiovasc Drugs. 2023 May;23(3):277-286. doi: 10.1007/s40256-023-00572-x. 
      Epub 2023 Feb 15.