Tumour, whole-blood, plasma and tissue concentrations of metformin in lung cancer patients. Br J Clin Pharmacol 2023 Mar;89(3):1027-1035
Date
09/28/2022Pubmed ID
36164710Pubmed Central ID
PMC9931625DOI
10.1111/bcp.15546Scopus ID
2-s2.0-85139674325 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
AIM: Metformin is used for the management of type 2 diabetes mellitus (T2DM) and is being tested clinically as an anticancer agent. Metformin concentrations safely achievable in human solid tissues including tumours are unknown. This study was designed to determine metformin concentration in tissue compartments as a function of dose to inform rational dosing in preclinical models and interpretation of clinical results."
METHODS: Subjects with solid tumours to be treated by resection and either (A) willingness to take metformin for 7-10 days before surgery or (B) taking metformin for T2DM were eligible. Whole blood, plasma, tumour, tumour-adjacent uninvolved tissue and subcutaneous adipose tissue were obtained for liquid chromatography with tandem mass spectrometry to measure metformin concentrations.
RESULTS: All subjects had primary lung tumours. Metformin dose was significantly correlated with drug concentrations in all tissues analysed. Intersubject metformin concentrations varied by over two orders of magnitude. Metformin concentrations were significantly higher in tumour tissues and lower in adipose tissues compared to other tissues. Concentrations in blood and plasma were significantly correlated with concentrations in solid tissues.
CONCLUSION: Metformin accumulates in cellular compartments. Concentrations observed in plasma, blood, lung and tumour tissues in subjects treated with US Food and Drug Administration-approved doses for T2DM are lower than those typically used in tissue culture studies. However, such tissue concentrations are in line with those found within cultured cells treated with supra-pharmacological doses of metformin. Given the large intersubject variability in metformin concentrations, it is imperative to determine whether there is an association between tissue metformin concentration and anticancer activity in humans.
Author List
Phillips JD, Pooler DB, Ness DB, Fay K, Tau S, Demidenko E, Hampsch RA, Lewis LD, Miller TWAuthor
Todd W. Miller PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adipose TissueDiabetes Mellitus, Type 2
Humans
Hypoglycemic Agents
Lung Neoplasms
Metformin
Plasma
